Apoptosis. 2015 Mar;20(3):327-35.

p27kip1 overexpression regulates VEGF expression, cell proliferation and apoptosis in cell culture from eutopic endometrium of women with endometriosis.

Gonçalves GA1Camargo-Kosugi CMBonetti TCInvitti ALGirão MJSilva IDSchor E.

 

Abstract

We hypothesized that p27(kip1) overexpression can regulate endometriosis cell proliferation, apoptosis and vascular endothelial growth factor (VEGF) expression in the endometrium. The overexpression of p27(kip1) was obtained by transduction of p27(kip1) in primary cultures of endometrium obtained from women with endometriosis tissue with gene therapy technology. First generation bicistronic adenovirus: AdCMVhp27IRESEGFP (Adp27) and AdCMVNull (AdNull) were engineered in order to induce p27(kip1) expression in endometrial cells primary culture. The effect of p27(kip1) overexpression was elucidated through the cell proliferation evaluation and the expression of the cell cycle-related proteins p16, p21, p27, and p53. Cell cycle and apoptosis in endometrial cells from women with and without endometriosis were also evaluated. The VEGF levels were evaluated 1 and 7 days after transduction. The experiments were performed using Immunofluorescence stainings and flow cytometry technique. The cell proliferation statistically diminished markedly following p27(kip1) overexpression in the endometriosis group. This process was accompanied, however, by a statistically significant modulation of the cell cycle-related proteins p16, p21, p27 and p53 markedly increase following p27(kip1) overexpression in the endometriosis group (p < 0.001) and an increase in apoptotic cells was observed. In the endometriosis group, significant downregulation of VEGF expression was observed 7 days after p27(kip1) overexpression, attaining levels strikingly similar to those observed in the control endometrial cells. The findings of this study showed a link between the cell cycle control protein (p27(kip1)) and angiogenesis (VEGF). Our results, also reinforces the background of endometrial dysfunction as part of the origin of endometriosis. We believe that better knowledge of endometrium milieu and the establishment of the link between different, previously describe, altered pathways in this tissue can facilitate future genetic cell therapy.

 

 

Menopause. 2015 Jun;22(6):616-26.

Diagnostic methods for fast-track identification of endometrial cancer in women with postmenopausal bleeding and endometrial thickness greater than 5 mm.

Dueholm M1Marinovskij EHansen ESMøller CØrtoft G.

Abstract

OBJECTIVE:

This study aims to evaluate the diagnostic efficiency of pattern recognition by transvaginal ultrasonography (TVS) and gel infusion sonography (GIS) for identifying endometrial pathology and to compare this setup with a standard setup of endometrial sampling (ES), hysteroscopy with pattern evaluation (HY(pattern)), or magnetic resonance imaging (MRI).

METHODS:

This study used a prospective cohort of 174 women with postmenopausal bleeding and endometrial thickness of 5 mm or greater. Resectoscopic biopsy (hysteroscopy with biopsy) samples or hysterectomy served as reference standard. Malignant and benign endometrial patterns were evaluated with TVS, GIS and HY(pattern) were then added. The efficiency of each diagnostic strategy, including ES and MRI findings (n = 83), was compared and evaluated against the reference standard.

RESULTS:

ES, TVS, GIS, and HY(pattern) had high diagnostic efficiency (area under the curve) for malignancy diagnosis (ES, 0.90; TVS, 0.88; GIS, 0.92; HY(pattern), 0.91). When insufficient samples were incorporated, ES was less efficient than the other techniques. ES was not more efficient in the subgroup of women without localized lesions than in the subgroup of women with localized lesions. MRI and HY(pattern) added limited efficiency, whereas hysteroscopy with biopsy was most efficient.

CONCLUSIONS:

As a first-line technique, pattern recognition on TVS, GIS, and HY(pattern) correctly identifies 9 of 10 women with malignancy and is superior to pattern recognition on ES when insufficient samples are included. Endometrial pattern evaluated with TVS and GIS is a fast and efficient first-line diagnostic tool that outperforms ES in women with or without localized lesions. Malignant patterns on TVS/GIS should warrant fast-track evaluation, whereas women with benign patterns may be selected for office or operative hysteroscopy. A fast-track diagnostic setup based on pattern recognition is presented.

 

 

PLoS One. 2014 Dec 23;9(12):

A low-testosterone state associated with endometrioma leads to the apoptosis of granulosa cells.

Ono YJ1Tanabe A1Nakamura Y1Yamamoto H1Hayashi A1Tanaka T1Sasaki H1Hayashi M1Terai Y1Ohmichi M1.

 

Abstract

Although endometriosis is suspected to be a cause of premature ovarian insufficiency (POI), the mechanism(s) underlying this process have not been elucidated. Recently, androgens were shown to promote oocyte maturation and to play a role in folliculogenesis. In addition, several reports have documented low testosterone levels in the follicular fluid obtained from endometriosis patients. We therefore examined whether the low levels of serum testosterone are associated with the apoptosis of granulosa cells in follicles obtained from endometriosis patients. Serum samples were collected from 46 patients with endometriosis and from 62 patients without endometriosis who received assisted reproductive therapy. Specimens of the ovaries obtained from 10 patients with endometrioma were collected using laparoscopy. The mean serum testosterone concentration in the patients with endometriosis was significantly lower than that observed in the patients without endometriosis. Furthermore, high expression of a pro-apoptotic Bcl-2 member, BimEL, in the follicles was found to be associated with a low serum testosterone level. We clarified the underlying mechanisms using a basic approach employing human immortalized granulosa cells derived from a primary human granulosa cell tumor, the COV434 cell line. The in vitro examination demonstrated that testosterone inhibited apoptosis induced by sex steroids depletion via the PI3K/Akt-FoxO3a pathway in the COV434 cells. In conclusion, we elucidated the mechanism underlying the anti-apoptotic effects of testosterone on granulosa cells, and found that a low-testosterone status is a potentially important step in the development of premature ovarian insufficiency in patients with endometriosis.

 

 

Arch Gynecol Obstet. 2015 Jul;292(1):225-9.

K-Ras 4A Transcript variant is up-regulated in eutopic endometrium of endometriosis patients during proliferative phase of menstrual cycle.

Shahrabi-Farahani M1Shahbazi SMahdian RAmini-Moghaddam S.

Abstract

AIMS:

K-Ras transcripts comprise two main isoforms: K-Ras 4A and K-Ras 4B, which act differently. The expression of both isoforms was reported in many human tissues. However, K-Ras 4B was the major expressed transcript variant. An increased expression of K-Ras 4B mRNA was reported in eutopic endometrium of endometriosis patients. In this way, we aimed to study the expression of K-Ras 4A transcript in eutopic endometrium related to endometriosis.

METHODS:

Employing exon4-flanking primers, K-Ras isoforms were simultaneously amplified in a RT-PCR reaction. Quantitative real-time PCR was performed using GAPDH as an internal control. K-Ras 4A transcript expression in eutopic endometrium was analyzed by ΔΔC T method.

RESULTS:

We identified existence of both of K-Ras 4A and K-Ras 4B in eutopic endometrium of patients and controls. Quantitative real-time analysis demonstrated that K-Ras 4A expression was 2.7-fold higher in endometriosis than non-endometriosis eutopic samples. Interestingly, this overexpression mainly occurs through the proliferative phase of menstrual cycle.

CONCLUSION:

The findings bring to light the eminent role of K-Ras 4A in endometriosis. This splice variant which is known for promoting apoptosis could be an effective factor in balance between proliferation and death of eutopic endometrial cells.

 

 

Adv Biomed Res. 2014 Nov 29;3:226

Study of association between promoter tumor necrosing factor alpha gene polymorphisms in -850T/C, -863 A/C, and endometriosis.

Mardanian F1Aboutorabi R2Jefride Y1Amini G3.

Abstract

BACKGROUND:

The purpose of this study was to determine whether variability in gene encoding for promoter of tumor necrosis factor participates to women differences in susceptibility to endometriosis.

MATERIALS AND METHODS:

The study involved 130 women; 65 endometriotic and 65 healthy control women. The blood samples were genotyped for -850 T/C and -863 C/A polymorphisms in TNF alpha gene promoter. Chi-square, odd ratio, and confidence interval 95% were used to evaluate genotypes and allele frequency differences between two groups.

RESULTS:

No significant differences in genotypes distribution of -850 T/C (P = 0.32) and 863 C/A (P = 0.34) polymorphisms were obtained between two groups.

CONCLUSION:

According to this study, these two polymorphisms have no risk or protective factor to develop endometriosis.

 

 

Reprod Sci. 2015 Sep;22(9):1083-7

Serum Polyunsaturated Fatty Acids and Endometriosis.

Hopeman MM1Riley JK1Frolova AI1Jiang H2Jungheim ES3.

 

Abstract

Polyunsaturated fatty acids (PUFAs) are fatty acids containing 2 or more double bonds, and they are classified by the location of the last double bond. Omega 3 (n-3) and omega 6 (n-6) PUFAs are obtained through food sources including fatty fish and seed/vegetable oils, respectively, and they are important to a number of physiologic processes including inflammation. Previous work demonstrates suppressive effects of n-3 PUFAs on endometriotic lesions in animal models and decreased risk of endometriosis among women with high n-3 PUFA intake. Thus, we sought to determine the relationship between circulating levels of PUFAs and endometriosis in women. To do this, we performed a cross-sectional study of serum PUFAs and clinical data from 205 women undergoing in vitro fertilization (IVF). Serum PUFAs were measured using liquid chromatography coupled to tandem mass spectroscopy and included n-3 PUFAs such as α-linolenic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid and n-6 PUFAs such as linoleic acid and arachidonic acid. Multivariable logistic regression was used to determine relationships between specific and total serum PUFAs and patient history of endometriosis. Women with high serum EPA levels were 82% less likely to have endometriosis compared to women with low EPA levels (odds ratio = 0.18, 95% confidence interval 0.04-0.78).

 

 

Am J Obstet Gynecol. 2015 Mar;212(3):304.e1-7.

Use of other treatments before hysterectomy for benign conditions in a statewide hospital collaborative.

Corona LE1Swenson CW2Sheetz KH3Shelby G3Berger MB2Pearlman MD2Campbell DA Jr3DeLancey JO2Morgan DM2.

Abstract

OBJECTIVE:

We sought to analyze use of alternative treatments and pathology among women who underwent hysterectomy in the Michigan Surgical Quality Collaborative.

STUDY DESIGN:

Perioperative hysterectomy data including demographics, preoperative alternative treatments, and pathology results were analyzed from 52 hospitals participating in the Michigan Surgical Quality Collaborative from Jan. 1 through Nov. 8, 2013. Women who underwent hysterectomy for benign indications including uterine fibroids, abnormal uterine bleeding (AUB), endometriosis, or pelvic pain were eligible. Pathology was classified as “supportive” when fibroids, endometriosis, endometrial hyperplasia, adenomyosis, adnexal pathology, or unexpected cancer were reported and “unsupportive” if these conditions were not reported. Multivariable analysis was done to determine independent associations with use of alternative treatment and unsupportive pathology.

RESULTS:

Inclusion criteria were met by 56.2% (n = 3397) of those women who underwent hysterectomy (n = 6042). There was no documentation of alternative treatment prior to hysterectomy in 37.7% (n = 1281). Alternative treatment was more likely to be considered among women aged <40 years vs those aged 40-50 and >50 years (68% vs 62% vs 56%, P < .001) and among women with larger uteri. Unsupportive pathology was identified in 18.3% (n = 621). The rate of unsupportive pathology was higher among women age <40 years vs those aged 40-50 and >50 years (37.8% vs 12.0% vs 7.5%, P < .001), among women with an indication of endometriosis/pain vs uterine fibroids and/or AUB, and among women with smaller uteri.

CONCLUSION:

This study provides evidence that alternatives to hysterectomy are underutilized in women undergoing hysterectomy for AUB, uterine fibroids, endometriosis, or pelvic pain. The rate of unsupportive pathology when hysterectomies were done for these indications was 18%.

 

 

Theriogenology. 2015 Apr 1;83(6):988-94.

Effects of vascular elastosis on uterine blood flow and perfusion in anesthetized mares.

Esteller-Vico A1Liu IK2Vaughan B3Steffey EP3Brosnan RJ3.

 

Abstract

In the uterus of the mare, data obtained using transrectal Doppler ultrasonography indicate that uterine blood flow (UBF) is dynamic and changes throughout the estrous cycle. Degenerative lesions in the uterus are associated with subfertility and infertility. Among these lesions, vascular elastosis has been reported in aged, multiparous, and infertile mares. Angiosis of the uterine vasculature could potentially compromise UBF. The objectives of this experiment are to determine levels of UBF and perfusion of reproductively healthy mares and compare them to levels of subfertile/infertile mares affected by uterine vascular elastosis. Twenty mares were classified on the basis of degree of vascular degeneration and stage of cycle. A fluorescent microsphere technique was used to measure reproductive organ perfusion, where microspheres were injected into the left ventricle of the heart and became trapped in capillary beds in proportion to blood flow and tissue perfusion. The reproductive tract was removed, sectioned, and the fluorescent intensity evaluated to measure blood flow and perfusion. Additionally, full-thickness samples of the uterine wall were examined postmortem to further assess the degree of vascular degeneration in all layers of uterine wall. The mean value of uterine perfusion for the control mares during estrus (n = 5) was higher (P < 0.01) than that during diestrus (n = 5); 17.6 and 11.9 mL/min/100g, respectively. For the subfertile/infertile mares, the mean value of tissue perfusion was not different (P > 0.05) during estrus (n = 5) and diestrus (n = 5); 5.9 and 7.2 mL/min/100g, respectively. Uterine perfusion in subfertile/infertile mares affected by elastosis was lower than that of control mares during both estrus (P < 0.01) and diestrus (P < 0.01). The differences in baseline levels of perfusion between the control and elastosis groups indicate that elastosis of the uterine vasculature is associated with decreased uterine perfusion during both phases of the estrous cycle. In the uterus, a compromise in UBF could have implications in endometrial glandular development, postbreeding endometritis, uterine clearance, development of the conceptus, and overall fertility.

 

 

J Obstet Gynaecol. 2015;35(7):711-5

Arterial stiffness is increased in young women with endometriosis.

Tani A1Yamamoto S1Maegawa M2Kunimi K1Matsui S1Keyama K1Kato T1Uemura H3Kuwahara A1Matsuzaki T1Yasui T4Kamada M5Soeki T6Sata M6Irahara M1.

 

Abstract

Endometriosis is a chronic gynaecological disorder that is accompanied by inflammation and oxidative stress. Atherosclerosis has a long subclinical progression in arteries of children and young adults decades before overt clinical manifestations of the disease. In this study, we determined arterial stiffness by measuring brachial-ankle pulse wave velocity (baPWV) in women with endometriosis to assess the presence of subclinical atherosclerosis. We also measured markers of inflammation and oxidative stress in women with endometriosis. baPWV in women with endometriosis aged over 30 years was significantly higher than that in women without endometriosis aged over 30 years (p < 0.05), but not in women aged less than 30. Serum high-sensitivity C-reactive protein level in women with endometriosis was significantly higher than that in controls (p < 0.05). Young women with endometriosis show significantly increased arterial stiffness, suggesting that women with endometriosis need to be cautious of the future onset of atherosclerosis.

 

 

J Minim Invasive Gynecol. 2014 Nov-Dec;21(6):1080-5.

Urodynamic evaluation and anorectal manometry pre- and post-operative bowel shaving surgical procedure for posterior deep infiltrating endometriosis: a pilot study.

Spagnolo E1Zannoni L1Raimondo D1Ferrini G1Mabrouk M2Benfenati A1Villa G1Bertoldo V1Seracchioli R3.

Abstract

STUDY OBJECTIVE:

To analyze bowel and urinary function in patients with posterior deep infiltrating endometriosis (DIE) >30 mm in largest diameter at transvaginal ultrasound before and after surgical nerve-sparing excision.

DESIGN:

Prospective observational study (Canadian Task Force classification III).

SETTING:

Tertiary care university hospital in Bologna, Italy.

PATIENTS:

Twenty-five patients with posterior DIE were included in the study between June 2011 and December 2012. Patients did not receive hormone therapy for at least 3 months before and 6 months after surgery.

INTERVENTIONS:

Patients underwent urodynamic studies and anorectal manometry before and after nerve-sparing laparoscopic excision of the posterior DIE nodule.

MEASUREMENTS AND MAIN RESULTS:

Intestinal and urinary function was evaluated in patients with bulky posterior DIE using urodynamic and anorectal manometry. Results of urodynamic studies and anorectal manometry were similar before and after nerve-sparing surgical excision of the posterior DIE nodule. Urodynamic studies demonstrated a high prevalence of voiding dysfunction, whereas anorectal manometry showed no reduction in rectoanal inhibitory reflex and hypertone of the internal anal sphincter.

CONCLUSIONS:

Patients with posterior DIE >30 mm in greatest diameter demonstrate preoperative dysfunction at urodynamic study and anorectal manometry, probably due to DIE per se. The nerve-sparing surgical approach seems not to influence the motility or sensory capacity of the bladder and the rectosigmoid colon.

 

 

J Clin Endocrinol Metab. 2015 Mar;100(3):E433-42.

Decreased Notch pathway signaling in the endometrium of women with endometriosis impairs decidualization.

Su RW1Strug MRJoshi NRJeong JWMiele LLessey BAYoung SLFazleabas AT.

Abstract

CONTEXT:

Endometriosis is a common gynecological disease affecting one in 10 women of reproductive age and is a major cause of pelvic pain and impaired fertility. Endometrial stromal cells of women with endometriosisexhibit a reduced response to in vitro decidualization. NOTCH1 is critical for decidualization of both mouse and human uterine stromal cells.

OBJECTIVE:

This study aimed to determine whether decidualization failure in women with endometriosis is a consequence of impaired Notch signaling.

SETTING AND DESIGN:

We investigated expression levels of Notch signaling components in the endometrium of women and baboons with or without endometriosis. We identified NOTCH1-regulated genes during decidualization of human uterine fibroblast (HuF) cells by microarray and quantified their expression levels in in vitro-decidualized endometrial stromal cells isolated from women with or without endometriosis.

RESULTS:

Notch signaling receptors NOTCH1 and NOTCH4, ligands JAGGED2 and DLL4, as well as direct target genes HES5 and HEY1 were decreased in the eutopic endometrium of women and baboons with endometriosis. Notch signaling was decreased in stromal cells isolated from women with endometriosis, which was associated with impaired in vitro decidualization. Genes that were down-regulated by NOTCH1 silencing in decidualized HuF cells were also decreased in decidualized endometrial stromal cells of women with endometriosis. FOXO1 acts as a downstream target of Notch signaling and endometriosis is associated with decreased expression of NOTCH1-regulated, FOXO1-responsive genes during decidualization.

CONCLUSIONS:

Decreased Notch signaling is associated with endometriosis and contributes to impaired decidualization through the down-regulation of FOXO1.

 

 

Clin Nucl Med. 2015 Feb;40(2):186-8.

Increased 18F-FDG uptake of widespread endometriosis mimicking ovarian malignancy.

Ge J1Zuo CGuan YZhang X.

 

Abstract

Endometriosis is a benign disease characterized by the implantation of functional endometrial tissue in ectopic locations. We present a case of a 42-year-old woman with widespread endometriosis that mimicked ovarian malignancy on FDG PET/CT. Increased FDG uptake was observed not only in the right ovary, but also in the liver capsule, perihepatic nodules, greater omentum, and the mesentery. This case indicates that widespread endometriosis may be a cause of multiple FDG uptakes in women of reproductive age and should always be kept in mind in the differential diagnoses of suspicious malignancy.

 

 

Clin Nucl Med. 2015 Feb;40(2):184-5.

18F-FDG PET/CT findings of a recurrent adenocarcinoma arising from malignant transformation of abdominal wall endometriosis.

Jiang M1Chen PSun LHuang QWu H.

 

Abstract

Abdominal wall endometriosis (AWE) is defined as endometrial tissue located superficial to the peritoneum, which usually develops in a surgical scar of cesarean delivery. Malignant transformation of AWE is a very rare disease. The most frequent histotype of malignancy developing from AWE is endometrioid adenocarcinoma. We present F-FDG PET/CT findings in a 37-year-old woman with a recurrent adenocarcinoma arising from malignant transformation of AWE, who underwent a repeat PET/CT scan because of a recurrent mass at the upper right side of the surgical incision after a previous cesarean delivery.

 

 

Colorectal Dis. 2015 Jun;17(6):536-41

How do patients score cosmesis after laparoscopic natural orifice specimen extraction colectomy?

Wolthuis AM1Meuleman C2Tomassetti C2D’Hooghe T2Fieuws S3de Buck van Overstraeten A1D’Hoore A1.

Abstract

AIM:

Laparoscopic colorectal resection results in improved cosmetic outcome and better presumed body image. Laparoscopic NOSE colectomy omits an incision for specimen extraction and is supposed to further improve postoperative cosmesis. This study aimed to assess the cosmetic benefit.

METHOD:

Forty-nine patients who underwent a NOSE colectomy for bowel endometriosis from September 2009 to September 2013 were matched for age, American Society of Anesthesiologists (ASA) grade and body mass index (BMI) with patients who underwent a conventional laparoscopic colectomy for the same indication. Patients were asked to complete a questionnaire consisting of a body scale and a cosmetic scale and the Patient Scar Assessment Questionnaire (PSAQ) including five subscales (appearance, symptoms, scar consciousness, satisfaction with appearance and satisfaction with symptoms).

RESULTS:

Patient demographics were similar between both groups. Patients were assessed at a median postoperative follow-up of 41 months in the NOSE colectomy group and 35 months in the conventional resection group. The median body image questionnaire score was 15 for NOSE colectomy and 18 for conventional resection (P = 0.027). The respective median PSAQ scores were 56 and 71 (P = 0.002). There was a good relationship between the PSAQ score and the body image questionnaire (Spearman correlation coefficient 0.82).

CONCLUSION:

Depending on the scoring system used, the cosmetic outcome may be better after NOSE colectomy than conventional laparoscopy in patients having surgery for endometriosis. The comprehensive body image questionnaire, being shorter and easier to use, could be a valid tool for assessing cosmesis after NOSE procedures.

 

 

Ginekol Pol. 2014 Oct;85(10):792-5.

Clear cell carcinoma derived from an endometriosis focus in a scar after a caesarean section–a case report and literature review.

Dobrosz ZPaleń PStojko RWłaszczuk PNiesłuchowska-Hoxha APiechuta-Kośmider I.

 

Abstract

Endometriosis is defined as the occurrence of endometrial glands and endometrial stromal cells outside their typical localization within the uterus. Malignant transformation of endometriosis foci in a scar after a caesarean section (cc) is very rare–until 2013 (in a span of 40 years), about 40 such cases have been described. In our article, we describe a case of a 42-year-old woman with a tumour localized in a scar after a caesarean section. The tumour was diagnosed as clear cell carcinoma derived from an endometriosis focus. The long time interval–17 years in average (from 3 to 39 years) between the surgery (cesarean section in most cases) and the tumor diagnosis is characteristic. In the case we describe, the patient was diagnosed 16 years after the endometriosisfocus in the scar had arised. Even though endometriosis is a benign lesion, it has many features distinctive for invasive carcinoma; it may itself undergo a malignant transformation as well as increase the risk of endometrial carcinoma or clear cell ovarian carcinoma. Maybe in future, more exhaustive studies will allow establishing a therapeutic protocol in patients with extra-ovarian malignant transformation of endometriosis foci.

 

 

 

Hum Fertil (Camb). 2015 Jun;18(2):128-33.

Glutathione S-transferase M1 and T1 gene polymorphisms and risk of endometriosis in Tunisian population.

Henidi B1Kaabachi SMbarik MZhioua AHamzaoui K.

Abstract

OBJECTIVE:

An association between endometriosis and the glutathione S-transferase M1 (GSTM1)- and GSTT1-related genes has been proposed on account of the detoxification properties of the GST enzymes. The aim of the present study was to investigate whether the polymorphisms and null mutations are associated with the susceptibility to endometriosis.

METHODS:

The study included 105 women with endometriosis and 150 healthy women with no laparoscopic evidence of disease. Genotyping of the GSTM1 and GSTT1 gene polymorphisms was performed by Multiplex-PCR.

RESULTS:

There was a significant association of GSTM1 null and GSTT1 null genotypes with endometriosis both when studied alone (P = 0.001 and P = 0.03, respectively) and in combination (P = 0.00002).

CONCLUSION:

The findings suggest that the GSTM1 and GSTT1 gene deficiency predisposes to endometriosisin a Tunisian population and can confer a significant increased risk when the GST null genotypes are combined.

 

 

Acta Pharm Hung. 2015;85(4):131-8.

Development possibilities of hormone-containing implants for gynecological applications: A review.

Szabó PKovács-Kiss DZelkó R.

 

Abstract

Implantable gynecological drug delivery devices are applied for contraceptive, hormone replacement purposes and for the treatments of other gynecological diseases, e.g. endometriosis. The review provides a comprehensive overview about the indications, advantages, limitation of application and the applied technologies of hormone-containing implants, as well. The study comprises the relevant patents and the recently published papers.

 

JNMA J Nepal Med Assoc. 2015 Jan-Mar;53(197):18-23.

Patterns of Lesions in Hysterectomy Specimens in a Tertiary Care Hospital.

Vaidya S1Vaidya SA2.

Abstract

INTRODUCTION:

Hysterectomy is one of the most common gynaecological procedures performed all over the world. The most frequent indications for hysterectomy are fibroids, abnormal uterine bleeding uterovaginal prolapse and endometriosis. The objective of this study was to present the histopathological patterns of various uterine and adnexal pathologies in the hysterectomy specimens and also to correlate its pre-operative clinical diagnosis with histopathology.

METHODS:

This is a two-year descriptive study of hysterectomy specimens carried out in the Department of Pathology, Patan Academy of Health Sciences (PAHS), Lalitpur, Nepal. Data of all the hysterectomy specimens collected during this period was analyzed.

RESULTS:

Out of the 533 cases, fibroid was the most common indication for hysterectomy that was seen in 229 (42.94%) cases followed by uterovaginal prolapse in 101 (18.93%) cases. Leiomyoma was the most common pathology reported in 250 (46.90%) hysterectomy specimens, followed by ovarian tumours in 95 (17.82%) cases. In 17.82% (95/533) cases, no pathology was seen. Overall, the pre-operative indications in 533 cases of hysterectomy were histopathologically verifiable in 487 (91.37%) cases.

CONCLUSIONS:

Though the histopathological examination correlates well with the pre-operative clinical diagnosis, a number of lesions were also encountered as pure incidental findings. Hence, it is mandatory that every hysterectomy specimen should be subjected to histopathological examination so as to ensure better post-operative management.

 

 

 

 

 

 

Tsitologiia. 2015;57(11):771-9.

CHARACTERISTIC OF ENDOMETRIAL MESENCHYMAL STEM CELLS IN CULTURE OBTAINED FROM PATIENT WITH ADENOMYOSIS.

Shilina MADomnina APKozhukharova IVZenin VVAnisimov SVNikolsky NNGrinchuk TM.

 

Abstract

Adenomyosis is form of endometriosis, common diseases of female reproductive system, which can lead to infertility in women. in this study we are obtained and characterized cell line endometrial mesenchymal stem cells from a patient with adenomyosis, and compare obtained cells with the cell line of healthy donor. Aim of this study was to assesses the extent of differences between cells from donor with adenomyosis and cells from healthy donor. Was established that compared lines had morphology like fibroblasts, were differentiated in adipocytes, were expressed mesenchymal markers and didn’t expressed haematopoietic markers. Cytogenetic analysis of differentially stained metaphase chromosomes on G-banding (passage 6-7) showed that healthy donor’s cells had predominantly normal karyotype. The cellular line from a patient with diagnosis of “adenomyosis” had a lot of cells with changes in karyotype’s structure. These changes were related with aneuploidy of cellular population and the presence non-random chromosomal breaks, often in chromosomes 7 and 11. Analysis of this data allows the cells from adenomyosis characterized physiological stability in culture and karyotypic instability with non-random involvement certain chromosomal set. The cellular line obtained from donor with adenomyosis showed signs destabilization of he genome, typical for cell transformation. Division of adenomyosis cells to the 26th passage is stopped and these cells entered into a phase of replicative aging. Based on this, we can conclude that founded karyotype’s hanges do not lead to transformation and immortalization of cells in vitro.

 

 

JBRA Assist Reprod. 2015 Nov 1;19(4):235-40.

Endometriosis Affects Oocyte Morphology in Intracytoplasmic Sperm Injection Cycles?

Borges E Jr1Braga DP1,2Setti AS3Vingris LS1Figueira RC1Iaconelli A Jr1.

Abstract

OBJECTIVE:

To identify associations between presence of endometriosis and oocyte defects, embryo developmental potential, and cycle outcomes.

METHODS:

This study looked into the impact of endometriosis on oocyte and embryo quality, and blastocyst formation probability. Endometriosis was also correlated with cycle characteristics. In order to avoid age-related bias, in the first analysis only patients aged 36 years or younger were included, and the cycles were split into endometriosis infertility cycles (n=431; 3172 oocytes) and other cycles (n=2510; 24480 oocytes).

RESULTS:

The number of retrieved oocytes (10.6±21.2 vs. 14.6±21.1, P<0.001), oocyte yield (68.1±20.0% vs. 70.6±19.6%, P=0.015), and embryos obtained (6.1±4.43 vs. 7.8±5.12, P<0.001) were lower among patients with endometriosis. Implantation rates (28.1%±38.9% vs. 33.9±42.7, P<0.001) were lower among patients with endometriosis, but fertilization, pregnancy, miscarriage and cycle cancelation rates were not different. There was a significant increase in the incidence of extra-cytoplasmic, but not intra-cytoplasmic, oocyte defects among patients with endometriosis. The quality of embryos (45.3% vs. 47.3%, P=0.037) collected from patients with endometriosis was lower, but blastocyst formation rates were unaltered.

CONCLUSION:

A possible explanation for the lower implantation rates seen in patients with endometriosis is the poorer quality of the oocytes and embryos observed in this group of patients.

 

 

Wiad Lek. 2015;68(3 pt 2):402-405.

Isolated vesical endometriosis – a case report.

Pliszkiewicz M1Siekierski BP1Pliszkiewicz M1.

Abstract

INTRODUCTION:

Although endometriosis affects up to 15% of the female population with childbearing potential, isolated endometriosis of the urinary tract is not a frequent occurrence, as it involves only 1 to 2% of all endometriosis patients. The chronic pelvic pain syndrome ultimately related to endometriosis is often both a diagnostic and therapeutic challenge Materials and methods: This paper presents the case of a female patient reporting with severe urinary symptoms. Following cystoscopy and ultrasonography investigations, a suspected endometrioid lesion of the urinary bladder has been evidenced. The patient-reported pain was rated using a 10-point visual analogue scale (VAS). The patient has not received pharmacotherapy.

RESULTS:

A partial laparoscopic full-thickness excision of the urinary bladder wall with the evidenced lesion has been performed. The urinary bladder wall has been sutured using two layers of sutures applied by laparoscopy. Postoperative histopathology examination revealed a deep infiltrating endometriosis lesion of the urinary bladder wall. Following surgery, the patient’s complaints have withdrawn completely, and no subsequent pharmacotherapy was instated.

DISCUSSION AND CONCLUSIONS:

Isolated endometriosis of the urinary tract, including the urinary bladder, is not a common pathology. Nevertheless, it should always be taken into account in patients with dysuria or symptoms suggestive of bladder malignancy. Total laparoscopic excision of the lesion remains the treatment of choice, and in most cases provides patients with complete withdrawal of symptoms, and only minimal incidence of recurrences, as well as limited risk of early and delayed complications.

 

 

 

Adv Gerontol. 2015;28(3):453-461.

Signal molecules of endometrium: gerontological and general pathhological aspects.

Grigorian IY1Linkova NS1,2Polyakova VO3Paltseva EM4Kozlov KL1.

 

Abstract

The review describes neuro-immuno-endocrine signal molecules expression in human endometrial cells in the normal conditions, in the pathology and during aging. Human endometrial cells synthesizes estrogen, progesterone, estradiol, progestin, cell adhesion molecules (integrines α1β1, α4β1, αVβ3, L-selectin, Е-catgerin, MUC1), grow factors (TGF, EGF, HB-EGF, IGF), cytokines (IL-1, IL-2, INF-α, IL-12, СХСL10, CXCL11, CXCR3), various immune cells markers (CD68, CD105, CD163, CD16, CD56, CD4, CD8), heat shock proteins (HSP60, HSP70, HSP90, VEGF, MMP). Changes of this molecules expression level are the base of the social significant diseases as endometriosis, endometrial cancer and infertility. Thus, the investigation of neuro-immuno-endocrine interactions in endometrial cells can be used for new drugs creating, in differential diagnostics of endometrial cancer and increasing of extracorporal fertilization success.

 

 

Int J Clin Exp Pathol. 2014 Oct 15;7(11):7752-9.

Expression of vascular endothelial growth factor C and anti-angiogenesis therapy in endometriosis.

Song WW1Lu H2Hou WJ2Xu GX2Zhang JH2Sheng YH2Cheng MJ3Zhang R2.

 

Abstract

Angiogenesis is an important pathogenesis of Endometriosis. Vascular endothelial growth factor C (VEGF-C) is one of the most important factor in the regulation of both normal and abnormal angiogenesis. Anti-angiogenic treatment of endometriosis is still in the exploratory stage. In this study, we investigate the relationship between VEGF-C and endometriosis, the therapeutic effects of Endostar in the rat endometriosis model. We then demonstrated that Immunohistochemical expression of VEGF-C was higher in endometriotic tissues than in control normal ovary tissues (P < 0.01) and higher in the endomertriosis grade III-IV than in endomertriosis grade I-II (P=0.013). In rat endometriosis model, we observed a significant reduction in the mean volume and weight of the endometriotic implants per rat in the treatment group as compared with the control group. By immunohistochemical evaluation, there was a significant reduction in VEGF-C expression after treatment in all areas examined. VEGF-C may be involved in the pathogenesis of endomertriosis by regulating the angiogenesis. Endostar has therapeutic effects of endometriosis lesions in the rat endometriosis model.

 

 

Int J Clin Exp Med. 2014 Nov 15;7(11):3853-8.

Stem cell and endometriosis: new knowledge may be producing novel therapies.

Yang J1Huang F1.

 

Abstract

The human endometrium is a dynamic tissue, which undergoes cycles of growth and regression with each menstrual cycle. Adult progenitor stem cells are likely responsible for this remarkable regenerative capacity; these same progenitor stem cells may also have an enhanced capacity to generate endometriosis if shed in a retrograde fashion. The progenitor stem cells reside in the uterus, and, however, may also travel from other tissues such as bone marrow to repopulate the progenitor population. Mesenchymal stem cells are also involved in the pathogenesis of endometriosis and may be the principle source of endometriosis outside of the peritoneal cavity when they differentiate into endometriosis in ectopic locations. The present short review mainly summarizes the latest observations contributing to the current knowledge regarding the presence and the potential contribution of stem cells in the etiology of endometriosis. All these data can have clinical implications and provide a basis for new potential therapeutic applications.

 

 

 

 

 

Clin J Pain. 2015 Nov;31(11):959-67.

Clinical Value of Serum Neuroplasticity Mediators in Identifying the Central Sensitivity Syndrome in Patients With Chronic Pain With and Without Structural Pathology.

Deitos A1Dussán-Sarria JASouza AdMedeiros LTarragô Mda GSehn FChassot MZanette SSchwertner AFregni FTorres ILCaumo W.

Abstract

BACKGROUND AND OBJECTIVES:

Central sensitivity syndrome (CSS) encompasses disorders with overlapping symptoms in a spectrum of structural pathology from persistent somatic nociception (eg, osteoarthritis) to absence of tissue injury such as in fibromyalgia, chronic tension-type headache, and myofascial pain syndrome. Likewise, the spectrum of the neuroplasticity mediators associated with CSS might present a pattern of clinical utility.

METHODS:

We studied the brain-derived neurotrophic factor (BDNF), tumor necrosis factor-α (TNF-α), and interleukins 6 (IL-6) and IL-10 in female patients with CSS absent of structural pathology (chronic tension-type headache [n=30], myofascial pain syndrome [n=29], fibromyalgia [n=22]); with CSS due to persistent somatic/visceral nociception (osteoarthritis [n=27] and endometriosis [n=32]); and in pain-free controls (n=37).

RESULTS:

Patients with CSS absent of structural pathology presented higher serum TNF-α (28.61±12.74 pg/mL) and BDNF (49.87±31.86 ng/mL) than those with persistent somatic/visceral nociception (TNF-α=17.35±7.38 pg/mL; BDNF=20.44±8.30 ng/mL) and controls (TNF-α=21.41±5.74 pg/mL, BDNF=14.09±11.80 ng/mL). Moreover, CSS patients absent of structural pathology presented lower IL levels. Receiver operator characteristics analysis showed the ability of BDNF to screen CSS (irrespective of the presence of structural pathology) from controls (cutoff=13.31 ng/mL, area under the curve [AUC]=0.86, sensitivity=95.06%, specificity=56.76%); and its ability to identify persistent nociception in CSS patients when experiencing moderate-severe depressive symptoms (AUC=0.81; cutoff=42.83 ng/mL, sensitivity=56.80%, specificity=100%). When the level of pain measured on the visual analog scale was <5 and moderate-severe depressive symptoms were observed TNF-α discriminated structural pathology in the chronic pain conditions (AUC=0.97; cutoff=22.11 pg/mL, sensitivity=90%, specificity=91.3%).

CONCLUSION:

Neuroplasticity mediators could play a role as screening tools for pain clinicians, and as validation of the complex and diffuse symptoms of these patients.

 

 

Clin Obstet Gynecol. 2015 Mar;58(1):76-92.

Adnexal masses in children and adolescents.

Kelleher CM1Goldstein AM.

 

Abstract

Adnexal masses in children encompass a variety of lesions of the ovaries and fallopian tubes, including ovarian cysts and tumors (benign or malignant), fallopian tube cysts and abscesses, paratubal cysts, and endometriomas. When developing a differential diagnosis for adnexal masses in childhood, the clinician must have a broad understanding of adnexal pathology and consider the patient’s age, presenting complaints, physical examination findings, and imaging results to generate a list of possible diagnoses and the appropriate treatment plan. We review the clinical presentation of these lesions and discuss the current recommendations for their management.

 

 

Clin Exp Obstet Gynecol. 2014;41(6):713-6.

Relation of red cell distribution width to the presence and severity of endometriosis.

Kurt RK1Dogan ACYesilyurt HKarateke AOkyay AG.

Abstract

AIM:

Although the exact pathogenesis of endometriosis is not known, it is proposed to be a chronic inflammatory disease. The asso- ciation between red cell distribution width (RDW) and inflammation is well established. Therefore, in the present study, the authors aimed to investigate the association between presence and severity of endometriosis and RDW.

MATERIALS AND METHODS:

Fifty endometriosis patients and 48 controls were included in the study. The endometriosis group was categorized in two subgroups as mild-to-moderate (n = 35) and moderate-to-severe disease (n = 15). CA-125 and RDW values of all participants were measured.

RESULTS:

Both RDW (17.7 ± 2.2 vs 14.9 ± 1.5, p < 0.001) and CA-125 (50.6 ± 35.1 vs 27.9 ± 4.8) levels were significantly higher in the endometriosis patients when compared to the control group. Moreover the authors found a significant positive correlation between RDW and CA-125 levels (r: 0.495, p < 0.001).

CONCLUSION:

The present study results demonstrated that RDW levels were significantly increased in endometrio- sis patients and associated with the severity of endometriosis.

 

 

Int J Med Sci. 2015 Jan 1;12(1):42-7

Effect of helixor A on natural killer cell activity in endometriosis.

Jeung IC1Chung YJ1Chae B1Kang SY1Song JY1Jo HH1Lew YO1Kim JH1Kim MR1.

Abstract

BACKGROUND AND AIM:

NK cells are one of the major immune cells in endometriosis pathogenesis. While previous clinical studies have shown that helixor A to be an effective treatment for endometriosis, little is known about its mechanism of action, or its relationship with immune cells. The aim of this study is to investigate the effects of helixor A on Natural killer cell (NK cell) cytotoxicity in endometriosis

MATERIALS AND METHODS:

We performed an experimental study. Samples of peritoneal fluid were obtained from January 2011 to December 2011 from 50 women with endometriosis and 50 women with other benign ovarian cysts (control). Peritoneal fluid of normal control group and endometriosis group was collected during laparoscopy. Baseline cytotoxicity levels of NK cells were measured with the peritoneal fluid of control group and endometriosis group. Next, cytotoxicity of NK cells was evaluated before and after treatment with helixor A. NK-cell activity was determined based upon the expression of CD107a, as an activation marker.

RESULTS:

NK cells cytotoxicity was 79.38±2.13% in control cells, 75.55±2.89% in the control peritoneal fluid, 69.59±4.96% in endometriosis stage I/II endometriosis, and 63.88±5.75% in stage III/IV endometriosis. A significant difference in cytotoxicity was observed between the control cells and stage III/IV endometriosis, consistent with a significant decrease in the cytotoxicity of NK cells in advanced stages of endometriosis; these levels increased significantly after treatment with helixor A; 78.30% vs. 86.40% (p=0.003) in stage I/II endometriosis, and 73.67% vs. 84.54% (p=0.024) in stage III/IV. The percentage of cells expressing CD107a was increased significantly in each group after helixor A treatment; 0.59% vs. 1.10% (p=0.002) in stage I/II endometriosis, and 0.79% vs. 1.40% (p=0.014) in stage III/IV.

CONCLUSIONS:

Helixor A directly influenced NK-cell cytotoxicity through direct induction of CD107a expression. Our results open new role of helixor A as an imune modulation therapy, or in combination with hormonal agents, for the treatment of endometriosis.

 

 

Front Biosci (Elite Ed). 2015 Jan 1;7:309-21.

Pathological functions of hypoxia in endometriosis.

Hsiao KY1Lin SC1Wu MH1Tsai SJ1.

 

Abstract

Endometriosis is one of the most common gynecological diseases that significantly reduce the life quality of affected women. Research results from the past decade clearly demonstrated that aberrant production of estrogen and cyclooxygenase-2-derived prostaglandin E2 play indispensable roles in the pathogenesis of this disease. However, the etiology of endometriosis remains obscure. Recent evidence reveals a new facet of endometriotic pathogenesis by showing that hypoxia induces the expression of many important downstream genes to regulate the implantation, survival, and maintenance of ectopic endometriotic lesions. These new findings shed lights on future investigations of delineating the etiology of endometriosis and designing new therapeutic strategy for endometriosis.

 

 

Diagn Interv Imaging. 2015 Apr;96(4):373-81.

Urinary endometriosis: MR imaging appearance with surgical and histological correlations.

Sillou S1Poirée S2Millischer AE3Chapron C4Hélénon O1.

Abstract

OBJECTIVES:

The goals of the study were to describe the MR imaging features of endometriosis of the urinary tract and identify those that suggest intrinsic involvement of ureteric wall.

MATERIALS AND METHODS:

Thirty-five women with proven urinary tract endometriosis and who had preoperative MR imaging between 2001 and 2011 were included retrospectively. MR images were intrepreted by one junior and one senior radiologists. To characterize the intrinsic parietal involvement, the ureteric circumference involved by the lesion of endometriosis was noted.

RESULTS:

Thirty-eight ureteric and 13 bladder lesions were analyzed. They were found in association in nine women. Ureteric lesions were bilateral in seven women. Of the 38 ureteric lesions, 27 were extrinsic and 11 intrinsic at histopathological analysis. Sixteen women with extrinsic lesions and 10 with intrinsic ones were correctly identified on MR imaging. When the ureter was included less than 360° in the lesion, extrinsic involvement was confirmed in 80% of cases.

CONCLUSION:

MR imaging appears to be more sensitive (91%vs 82%) but less specific (59% vs 67%) than surgery for the diagnosis of intrinsic form of ureteric location.

 

 

Cancer Cytopathol. 2015 Apr;123(4):253-7.

ARID1A is a useful marker of malignancy in peritoneal washings for endometrial carcinoma.

Nagymanyoki Z1Mutter GLHornick JLCibas ES.

Abstract

BACKGROUND:

ARID1A (AT-rich interactive domain 1A gene) has recently been identified as a novel tumor suppressor gene and one of the driver genes in endometrial carcinogenesis. Approximately 30% to 40% of endometrial carcinomas harbor mutations in the ARID1A gene, which results in complete loss of ARID1A protein expression. Although ARID1A aberrations are not restricted to endometrial cancer, the authors hypothesized that it might be a useful marker of malignancy in peritoneal washings for patients with endometrial cancer.

METHODS:

The cytology archive of Brigham and Women’s Hospital was searched to identify cell blocks from peritoneal washings that contained malignant or benign endometrial epithelium. From 2006 through 2013, 17 cases of endometrial carcinoma (EMCA) and 16 cases of endometriosis were identified. Surgical pathology reports and follow-up data were used to confirm the diagnoses. Immunohistochemistry for ARID1A was performed, and slides were scored as 0 (complete loss of staining) or 1 (retained staining) by 2 independent pathologists. The discordant cases were resolved by consensus. The two-tailed Fisher exact probability test was used to calculate statistical significance.

RESULTS:

Complete loss of ARID1A expression was found in 8 of 17 EMCA cases (47%) and none of the 16 endometriosis cases (0%) (P = .024). The concordance among the pathologists on first review was high (96.7%).

CONCLUSIONS:

The results of the current study demonstrated that ARID1A can be used in peritoneal washings to confirm malignancy in patients with EMCA. Complete loss of ARID1A expression by immunohistochemistry is highly specific for carcinoma, but retained expression is not informative.

 

 

Akush Ginekol (Sofiia). 2014;53(5):10-3.

Investigation of the role of tubal factor sterility in pelvic endometriosis.

Totev TTihomirova TTomov SGorchev G.

Abstract

OBJECTIVE:

To investigate frequency and characteristics of tubal factor in patients, diagnosed with endometriosis and sterility.

MATERIAL AND METHODS:

The invastigation includes 124 patients, diagnosed with endometriosis and history of sterility, who underwent diagnostic or operative laparoscopy for the period from 2008 to 2013. For each of the patients were registrated the results of chromopertubation, stage, according to rASRM, concomitant gynaecological diseases, sort and complexity grade of the operation.

RESULTS AND DISCUSSION:

According to the results, patients were divided in 3 groups, as each of them includes cases with similar prognosis and treatment models: 1. With maintained reproductive potentiality (75 patients); 2. With restricted reproductive potentiality, according to the uterine tubes (32 patients); 3. With absent reproductive potentiality, according to the uterine tubes (16 patients).

CONCLUSION:

The mini-invasive approach to women, suspicious for endometriosis and sterility, gives us the opportunity to make an accurate diagnosis and to determinate the severity of disease, to estimate the morphology and the presence of tubal occlusion, such as to accomplish the necessary range operative intervention of endometriosis lesions and other concomitant gynaecological diseases.

 

 

Obstet Gynecol. 2015 Jan;125(1):79-88

Influence of endometriosis on assisted reproductive technology outcomes: a systematic review and meta-analysis.

Hamdan M1Omar SZDunselman GCheong Y.

Abstract

OBJECTIVE:

To investigate the association of endometriosis on assisted reproductive technology (ART) outcomes and to review if surgical treatment of endometriosis before ART affects the outcomes.

DATA SOURCES:

We searched studies published between 1980 and 2014 on endometriosis and ART outcome. We searched MEDLINE, PubMed, ClinicalTrials.gov, and Cochrane databases and performed a manual search.

METHODS OF STUDY SELECTION:

A total of 1,346 articles were identified, and 36 studies were eligible to be included for data synthesis. We included published cohort studies and randomized controlled trials.

TABULATION, INTEGRATION, AND RESULTS:

Compared with women without endometriosis, women with endometriosis undertaking in vitro fertilization and intracytoplasmic sperm injection have a similar live birth rate per woman (odds ratio [OR] 0.94, 95% confidence interval [CI] 0.84-1.06, 13 studies, 12,682 patients, I=35%), a lower clinical pregnancy rate per woman (OR 0.78, 95% CI 0.65-0.94), 24 studies, 20,757 patients, I=66%), a lower mean number of oocyte retrieved per cycle (mean difference -1.98, 95% CI -2.87 to -1.09, 17 studies, 17,593 cycles, I=97%), and a similar miscarriage rate per woman (OR 1.26, 95% CI (0.92-1.70, nine studies, 1,259 patients, I=0%). Women with more severe disease (American Society for Reproductive Medicine III-IV) have a lower live birth rate, clinical pregnancy rate, and mean number of oocytes retrieved when compared with women with no endometriosis.

CONCLUSION:

Women with and without endometriosis have comparable ART outcomes in terms of live births, whereas those with severe endometriosis have inferior outcomes. There is insufficient evidence to recommend surgery routinely before undergoing ART.

 

 

Zhongguo Zhong Xi Yi Jie He Za Zhi. 2014 Nov;34(11):1288-91.

Kuntai capsule combined with gonadotropin releasing hormone agonist in treatment of moderate-severe endometriosis: a clinical observation.

Liu CQ1Qin ZXJiang FFHong TWang F.

Abstract

OBJECTIVE:

To observe the effect of Kuntai Capsule (KC), a Chinese patent medicine, in add-back therapy for gonadotropin-releasing hormone agonist (GnRH-a) treatment for moderate-severe endometriosis (EM).

METHODS:

Totally 100 patients suffering from stage III/IV EM, who were confirmed by laparoscopic surgery were randomly assigned to the GnRH-a group (A) and the KC combined GnRH-a group (B), 50 in each group. Patients in Group A were hypodermically injected with goserelin (3.6 mg), once per 4 weeks. Those in Group B additionally took KC, 4 pills each time, three times per day. The therapeutic course for all was 12 weeks. Serum levels of estradiol (E2), follicle stimulating hormone (FSH), bone gamma-carboxyglutamic-acid-containing proteins (BGP) were measured respectively. Kupperman Menopausal Index (KMI) and bone mineral density (BMD) of the lumbar vertebra were also compared between the two groups.

RESULTS:

Serum levels of E2 and FSH both significantly decreased in the two groups at week 12 of the treatment (P < 0.05), when compared with pre-treatment. Compared with before treatment in the same group, KMI increased in the two groups (P < 0.05). Compared with before treatment in the same group, BMI decreased in the two groups with no statistical difference (P > 0.05). Serum BGP increased after 12-week treatment (P < 0.05). Compared with Group A after treatment, serum levels of E2 and FSH both significantly increased in Group B (P < 0.05). There was no statistical difference in KMI between the two groups (P > 0.05). As for the incidence of menopausal symptoms, better effects in improving symptoms such as hot flashes, sleep disorders, and vaginal dryness were obtained in Group B than in Group A (P < 0.05). There was no significant difference in the post-pre-treatment difference of BMI between the two groups, but with statistical post-pre-treatment difference in the BGP level (P < 0.05).

CONCLUSIONS:

HKC combined GnRH-a could effectively reduce GnRH-a treatment induced partial low estrogen symptoms, improve increased serum BGP levels after GnRH-a therapy.

 

 

Hum Reprod. 2015 Mar;30(3):553-7.

Minimally invasive surgery when treating endometriosis has a positive effect on health and on quality of work life of affected women.

Wullschleger MF1Imboden S2Wanner J2Mueller MD2.

Abstract

STUDY QUESTION:

What is the effect of the minimally invasive surgical treatment of endometriosis on health and on quality of work life (e.g. working performance) of affected women?

SUMMARY ANSWER:

Absence from work, performance loss and the general negative impact of endometriosison the job are reduced significantly by the laparoscopic surgery.

WHAT IS KNOWN ALREADY:

The benefits of surgery overall and of the laparoscopic method in particular for treating endometriosis have been described before. However, previous studies focus on medical benchmarks without including the patient’s perspective in a quantitative manner.

STUDY DESIGN, SIZE, DURATION:

A retrospective questionnaire-based survey covering 211 women with endometriosis and a history of specific laparoscopic surgery in a Swiss university hospital, tertiary care center. Data were returned anonymously and were collected from the beginning of 2012 until March 2013.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Women diagnosed with endometriosis and with at least one specific laparoscopic surgery in the past were enrolled in the study. The study investigated the effect of the minimally invasive surgery on health and on quality of work life of affected women. Questions used were obtained from the World Endometriosis Research Foundation (WERF) Global Study on Women’s Health (GSWH) instrument. The questionnaire was shortened and adapted for the purpose of the present study.

MAIN RESULTS AND THE ROLE OF CHANCE:

Of the 587 women invited to participate in the study, 232 (232/587 = 40%) returned the questionnaires. Twenty-one questionnaires were excluded due to incomplete data and 211 sets (211/587 = 36%) were included in the study. Our data show that 62% (n = 130) of the study population declared endometriosis as influencing the job during the period prior to surgery, compared with 28% after surgery (P < 0.001). The mean (maximal) absence from work due to endometriosis was reduced from 2.0 (4.9) to 0.5 (1.4) hours per week (P < 0.001). The mean (maximal) loss in working performance after the surgery averaged out at 5.7% (12.6%) compared with 17.5% (30.5%) before this treatment (P < 0.001).

LIMITATIONS, REASONS FOR CAUTION:

The mediocre response rate of the study weakens the representativeness of the investigated population. Considering the anonymous setting a non-responder investigation was not performed. A bias due to selection, information and negativity effects within a retrospective survey cannot be excluded, although study-sensitive questions were provided in multiple ways. The absence of a control group (sham group; e.g. patients undergoing specific diagnostic laparoscopy without treatment) is a further limitation of the study.

WIDER IMPLICATIONS OF THE FINDINGS:

Our study shows that indicated minimally invasive surgery has a clear positive effect on the wellbeing and working performance of women suffering from moderate to severe endometriosis. Furthermore, national net savings in indirect costs with the present number of surgeries is estimated to be €10.7 million per year. In an idealized setting (i.e. without any diagnosis delay) this figure could be more than doubled.

STUDY FUNDING/COMPETING INTERESTS:

The study was performed on behalf of the University Hospital of Bern (Inselspital) as one of the leading Swiss tertiary care centers. The authors do not declare any competing interests.

 

 

Obstet Gynecol. 2015 Feb;125(2):397-405.

Unexpected gynecologic malignancy diagnosed after hysterectomy performed for benign indications.

Mahnert N1Morgan DCampbell DJohnston CAs-Sanie S.

Abstract

OBJECTIVE:

To define the incidence of unexpected gynecologic malignancies among women who underwent hysterectomy for benign indications.

METHODS:

We conducted a data analysis of hysterectomy cases from a quality and safety database maintained by the Michigan Surgical Quality Collaborative, a statewide group of hospitals that voluntarily reports perioperative outcomes. Cases were abstracted from January 1, 2013, through December 8, 2013. Benign preoperative surgical indications included pelvic mass, family history of cancer, hyperplasia without atypia, prolapse, endometriosis, pelvic pain, abnormal uterine bleeding, or leiomyomas. Women with a surgical indication of cancer, cervical dysplasia, or hyperplasia with atypia were excluded.

RESULTS:

During the study period, 7,499 women underwent a hysterectomy and 85.24% (n = 6,360) were performed for benign indications. The incidence of unexpected gynecologic malignancy among hysterectomies performed for benign indications was 2.7% (n = 172) and included ovarian, peritoneal, and fallopian tube cancer (n = 69 [1.08%]), endometrial cancer (n = 65 [1.02%]), uterine sarcoma (n = 14 [0.22%]), metastatic cancer (n = 13 [0.20%]), and cervical cancer (n = 11 [0.17%]). The most common indications for hysterectomy were leiomyomas and abnormal uterine bleeding. There was no difference in the mean age (46.86 ± 10.57 compared with 47.0 ± 10.76 years, P = .96) of women with unexpected sarcoma compared with benign disease. Women with unexpected sarcoma were more likely to have a history of venous thromboembolism and preoperative blood transfusion, but this did not reach statistical significance.

CONCLUSION:

The 2.7% incidence of unexpected gynecologic malignancy includes a 0.22% incidence of uterine sarcoma and 1.02% incidence of endometrial cancer. No reliable predictors of uterine sarcoma exist and caution is warranted in preoperative planning for hysterectomy.

 

 

J Minim Invasive Gynecol. 2015 Mar-Apr;22(3):363-72.

Effect of hemostatic method on ovarian reserve following laparoscopic endometrioma excision; comparison of suture, hemostatic sealant, and bipolar dessication. A systematic review and meta-analysis.

Ata B1Turkgeldi E2Seyhan A3Urman B2.

 

Abstract

We reviewed the literature to determine whether different hemostatic methods used following laparoscopic endometrioma excision have differing effects on ovarian reserve. We performed a systematic literature search using the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and Ovid MEDLINE In-Process & Other Non-Indexed Citations databases to identify studies comparing the rate of change in levels of serum anti-Müllerian hormone (AMH) at 3 months after laparoscopic endometrioma excision using bipolar dessication (BD) or suturing/application of a hemostatic sealant (HS) for hemostasis. Abstracts of the annual meetings of the American Society of Reproductive Medicine, the European Society of Human Reproduction and Embryology, and the American Association of Gynecological Laparoscopists were searched as well. A total of 712 articles were identified, of which 6 were included in the qualitative analysis. Four studies involving 213 women were included in the meta-analysis. Our qualitative analysis suggested that BD is more detrimental to ovarian reserve than alternative hemostatic methods. There is moderate-quality evidence favoring HS and low-quality evidence favoring sutures over BD. The meta-analysis also showed that alternative hemostatic methods are associated with significantly less decline in ovarian reserve compared with BD. The mean decline in serum AMH levels was 6.95% less with alternative hemostatic methods than with BD (95% CI, -13.0% to -0.9%; p = .02) at 3 months after surgery. According to the best available evidence, the use of BD should be cautiously limited, even avoided when possible, during endometrioma excision in women who desire to have children.

 

 

Exp Biol Med (Maywood). 2015 Sep;240(9):1177-82.

The association between vascular endothelial growth factor (VEGF) +405G>C genetic polymorphism and endometriosis.

Fang F1Gong L2Wang X2Zhang L2.

 

Abstract

The vascular endothelial growth factor (VEGF) is one of the most important candidate genes for the development of endometriosis, and VEGF genetic polymorphisms might be potentially associated with endometriosis risk. However, the results still remain controversial. The objective of this study aimed to perform a comprehensive meta-analysis to explore a better understanding of the effects of VEGF +405G>C genetic polymorphism on the risk of endometriosis. A total of eleven eligible studies were eventually identified in this meta-analysis, including 2829 endometriosis cases and 2947 controls. In the overall analysis, no significant association between the VEGF +405G>C genetic polymorphism and the risk of endometriosis was detected in all genetic models (for homozygote comparison [CC versus vs. GG]: OR = 1.21, 95% CI 0.67-2.19, P = 0.537; for heterozygote comparison [CG vs. GG]: OR = 1.16, 95% CI 0.86-1.56, P = 0.348; for dominant comparison CC/CG vs. GG: OR = 1.10, 95% CI 0.93-1.30, P = 0.263; for recessive comparison [CC vs. CG/GG]: OR = 1.03, 95% CI 0.73-1.47, P = 0.857; allele comparison [C vs. G]: OR = 0.99, 95% CI 0.70-1.40, P = 0.962). In the subgroup analysis by ethnicities, there was no significant association between VEGF +405G>C genetic polymorphism and endometriosis risk in Asians and/or Caucasians under all genetic models (all P-values >0.05). No publication bias was observed in this study. This meta-analysis supports that the VEGF +405G>C genetic polymorphism is not significant associated with the risk of endometriosis.

 

 

Hum Reprod. 2015 Mar;30(3):558-68.

Recurrences and fertility after endometrioma ablation in women with and without colorectal endometriosis: a prospective cohort study.

Roman H1Quibel S2Auber M2Muszynski H2Huet E3Marpeau L2Tuech JJ3.

Abstract

STUDY QUESTION:

What are the recurrence and pregnancy rates in women managed for ovarian endometrioma by ablation using plasma energy with and without associated surgery for colorectal endometriosis?

SUMMARY ANSWER:

Concomitant management of colorectal endometriosis does not impact either risk of recurrences or probability of pregnancy in women managed for endometrioma ablation using plasma energy.

WHAT IS KNOWN ALREADY:

No consensus exists on how best to manage patients presenting with ovarian endometriomas and colorectal endometriosis, in terms of impact on fertility preservation and recurrence rates.

STUDY DESIGN, SIZE, DURATION:

A prospective series of consecutive patients managed for ovarian endometriomas by ablation using plasma energy, over a period of 48 consecutive months. The study included patients with associated colorectal endometriosis (n = 52) and those who were free of colorectal localizations of the disease (n = 72). No women were lost to follow-up.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

The 124 women included in this study were managed for either unilateral or bilateral ovarian endometriomas using plasma energy at a university tertiary care center. Recurrences and pregnancy rate were compared in patients with and without colorectal endometriosis. The minimum length of follow-up was 1 year. Cyst recurrences were assessed using pelvic ultrasound and magnetic resonance imaging. Kaplan-Meier and actuarial life-table analysis were used to estimate the recurrence-free survival curve and the probability of pregnancy. The Cox model was used to assess independent predictive factors for recurrences. Pregnancy likelihood and independent predictors were estimated using a regression logistic model.

MAIN RESULTS AND THE ROLE OF CHANCE:

Mean follow-up was 32 ± 18 months. Forty-eight patients (40.3%) were presumed infertile and attended an assisted reproductive techniques (ART) center. Eighteen patients presented with a recurrence (14.5%). Bilateral localization of endometriomas was the only factor independently related to an increased risk of recurrences [hazard ratio 3.3, 95% confidence interval (CI) 1.2-9.4]. Of the 83 women wishing to conceive (66.9%), 51 became pregnant (61.4%) and 33 of these pregnancies were spontaneous (64.7%). The rates of pregnancy were 65.8% for the group of patients with associated colorectal endometriosis and 57.8% for controls (P = 0.50). Age over 35 years was the only independent factor for which association with pregnancy rates approached the significance threshold (adjusted odds ratio 0.35, 95% CI 0.12-1, P = 0.06).

LIMITATIONS, REASONS FOR CAUTION:

The study sample size may be insufficient to reveal statistically significant differences related to risk factors which have low impact on the probability of recurrence and pregnancy. Data on ovarian reserve before and after the procedure was not available in all patients, which would have added to our results and the discussion about treatment of endometrioma in general.

WIDER IMPLICATIONS OF THE FINDINGS:

Concomitant management of colorectal endometriosis does not impact either risk of recurrences or the probability of pregnancy in women having benefited from ovarian endometrioma ablation using plasma energy. Moreover, surgical management of colorectal and ovarian endometriosis may allow spontaneous conception in one out of three patients, thus reducing expenses related to ART management.

STUDY FUNDING/COMPETING INTERESTS:

No financial support was received for this study. Horace Roman reports personal fees for participating in a symposium and masterclass presenting his experience in the use of PlasmaJet.

 

 

J Obstet Gynaecol Can. 2014 Nov;36(11):1002-1009.

Pelvic floor tenderness in the etiology of superficial dyspareunia.

Yong PJ1Mui J1Allaire C1Williams C1.

Abstract

OBJECTIVE:

To calculate the prevalence of pelvic floor tenderness in the population of women with pelvic pain and to determine its implications for symptoms of pelvic pain.

METHODS:

We conducted a retrospective review of patients with pelvic pain at a tertiary referral centre. Pelvic floor tenderness was defined as levator ani tenderness on at least one side during single digit pelvic examination. The prevalence of pelvic floor tenderness in this cohort of women with pelvic pain was compared with the prevalence in a cohort of women without pain attending a gynaecology clinic. In the women with pelvic pain, multiple regression was performed to determine which variables were independently associated with pelvic floor tenderness.

RESULTS:

The prevalence of pelvic floor tenderness was 40% (75/189) in the cohort with pelvic pain, significantly greater than the prevalence of 13% (4/32) in the cohort without pain (OR 4.61; 95% CI 1.55 to 13.7, P = 0.005). On multiple logistic regression, superficial dyspareunia (OR 4.45; 95% CI 1.86 to 10.7, P = 0.001), abdominal wall pain (OR 4.04; 95% CI 1.44 to 11.3, P = 0.005), and bladder base tenderness (OR 4.65; 95% CI 1.87 to 11.6, P = 0.001) were independently associated with pelvic floor tenderness. Pelvic floor tenderness was similarly present in women with or without underlying endometriosis.

CONCLUSION:

Pelvic floor tenderness is common in women with pelvic pain, with or without endometriosis, and is a contributor to superficial dyspareunia. Pelvic floor tenderness was also associated with abdominal wall pain and bladder base tenderness, suggesting that nervous system sensitization is involved in the etiology of pelvic floor tenderness.

 

 

 

Fertil Steril. 2015 Mar;103(3):738-43.

Second surgery for recurrent endometriomas is more harmful to healthy ovarian tissue and ovarian reserve than first surgery.

Muzii L1Achilli C2Lecce F2Bianchi A3Franceschetti S2Marchetti C2Perniola G2Panici PB2.

Abstract

OBJECTIVE:

To evaluate the excised specimen with histologic analysis and to assess the antral follicle count (AFC) at follow-up. This is to determine whether excisional surgery for recurrent endometriomas is more harmful to ovarian tissue and to the ovarian reserve than first surgery.

DESIGN:

Prospective controlled study.

SETTING:

University hospital.

PATIENT(S):

Consecutive patients with pelvic pain and/or infertility undergoing laparoscopic excision of a monolateral ovarian endometrioma for the first time (17 patients) or for recurrence after previous surgery (11 patients).

INTERVENTION(S):

Laparoscopic excision of ovarian endometrioma and ultrasonographic evaluation 3 months after surgery.

MAIN OUTCOME MEASURE(S):

Cyst wall histologic evaluation (specimen thickness, presence and morphology of ovarian tissue) and evaluation of ovarian reserve with AFC and ovarian volumes of both the operated and contralateral, nonoperated ovary at follow-up.

RESULT(S):

The cyst wall specimen was significantly thicker in the recurrent endometrioma group than in the first surgery group (1.7 ± 0.3 mm vs. 1.1 ± 0.3 mm). Both main components of the cyst specimen (i.e., endometriosistissue and ovarian tissue) were more represented in the recurrent endometrioma group than in the first surgery group. At sonographic follow-up, the operated ovary had a significantly lower AFC and volume than the contralateral nonoperated ovary in the recurrent endometrioma group, but not in the primary surgery group.

CONCLUSION(S):

Surgery for recurrent endometriomas is associated with evidence of a higher loss of ovarian tissue and is more harmful to the ovarian reserve evaluated by AFC and ovarian volume, if compared with endometriomas operated for the first time. Indications to surgery for recurrent endometriomas should be reconsidered with caution.

 

 

Eur J Obstet Gynecol Reprod Biol. 2015 Feb;185:131-5

Usefulness of CA125 in the differential diagnosis of uterine adenomyosis and myoma.

Kil K1Chung JE1Pak HJ1Jeung IC1Kim JH1Jo HH1Kim MR2.

Abstract

OBJECTIVES:

To evaluate the usefulness of CA125 levels in the differential diagnosis of adenomyosis and myoma. This has been addressed by few, if any, previous studies.

STUDY DESIGN:

Preoperative serum CA125 levels were measured in 2149 women who were diagnosed at total hysterectomy as having adenomyosis, myoma, endometriosis, and/or normal pelvis. Their medical records were retrieved and reviewed.

RESULTS:

The mean serum CA125 level in the adenomyosis patients was significantly greater than that in the patients diagnosed with myoma (65.21±96.60 U/mL vs.12.86±14.23 U/mL, respectively; P<0.001). In the differential diagnosis of adenomyosis and myoma, the cut-off serum CA125 level with the highest accuracy (78.8%) and highest diagnostic value (61.2%) was 19 U/mL. Using this cut-off value, the negative predictive value was 69.5%, and the positive predictive value was 76.5%. These results are clearly superior to those of the empirical single cut-off value of 35 U/mL. Receiver operating characteristic curve analysis revealed the area under the curve for differentiating adenomyosis from myoma was 0.776, indicating good diagnostic performance.

CONCLUSION:

In the differential diagnosis of adenomyosis and myoma, cut-off values for CA125, particularly the cut-off value of 19 U/mL, provide improved diagnostic performance. Serum CA125 testing can be performed during the initial screening of women with possible adenomyosis to differentiate this condition from myoma, although the diagnostic accuracy of using CA125 testing alone is limited.

 

 

Int J Biochem Cell Biol. 2015 Mar;60:19-22.

New evidence in endometriosis.

Signorile PG1Baldi A2.

 

Abstract

Endometriosis is a recurrent and benign gynecological disorder characterized by the presence of endometrial tissue outside the cavity of the uterus. It is one of the most common diseases in the gynecological field, affecting about 10% of the female population in reproductive age. Despite this, its pathogenesis is still unacknowledged, there is a lack of early diagnostic markers and current therapies are only symptomatic. Considering the relevant health problems caused by endometriosis, all new information on this disease may have important clinical implications. The aim of this article is to summarize the latest advances in the pathogenesis, diagnosis and therapy of endometriosis that have recently been proposed by our research group. The possible clinical implications of these findings will be discussed.

 

Can Assoc Radiol J. 2015 May;66(2):115-20.

Spontaneous T1-Hyperintensity Within an Ovarian Lesion: Spectrum of Diagnoses.

Peyrot H1Montoriol PF2Canis M3.

 

Abstract

Whenever elevated signal intensity is displayed at magnetic resonance imaging (MRI) within an ovarian lesion on unenhanced T1-weighted sequences, some specific diagnoses should be considered because only 3 main components may be responsible for this T1-hyperintensity at MRI: fat, blood products, and proteinaceous or mucinous material. The associated clinical data and concomitant use of T2-weighted sequences and fat-saturation techniques is mandatory to make this tissue characterization possible. The goal of this pictorial review is to provide a simple radiologic reasoning and the differential diagnoses to consider in the presence of spontaneous elevated signal intensity on T1-weighted sequences within a cystic or solid ovarian tumour.

 

 

J Minim Invasive Gynecol. 2015 May-Jun;22(4):535.

Use of narrowband imaging for the detection of endometriosis.

Pastorfide G1Fong YF2.

Abstract

STUDY OBJECTIVE:

To show a new technique using narrowband imaging for the detection of endometriosis.

DESIGN:

A step-by-step illustration of the difference in visualization of endometriosis using a visible light spectrum laparoscope compared with a narrowband imaging light source.

SETTING:

Radical excision of endometriosis is considered the best treatment to control the disease extent and symptoms of endometriosis. Therefore, it is imperative that all endometriotic lesions are recognized and identified in order to thoroughly remove them. A narrowband imaging system enhances the visualization of capillary vessels and microstructures containing blood hemoglobin on the mucosal surface. It makes use of 415- and 540-nm filters that are strongly absorbed by blood hemoglobin. In this manner, microvessels, which are not clearly seen by conventional light, are enhanced. With the inherent neovascularization noted in endometriosis, endometriotic lesions may be more recognizable. Clear vesicular lesions of endometriosis are glandular excrescences, which are early signs of recurrent inflammation from endometriosis with accompanying angiogenesis. These are more pronounced under narrowband imaging.

INTERVENTIONS:

The use of the visible light spectrum contrasted with narrowband imaging that changes the normal color contrasts of the endoscopic image in the different areas of the pelvic cavity.

MEASUREMENTS AND MAIN RESULTS:

Narrowband imaging is helpful as an additional modality for the identification of endometriosis. In particular, clear vesicular lesions of endometriosis, which are not as evident under the visible light spectrum, are more pronounced under narrowband imaging. Its strength lies in its usefulness in the treatment of patients with endometriosis with symptoms of pain. It is especially useful for those with marked symptoms but, on first glance at laparoscopy, seems to have minimal disease. Narrowband imaging enhances the endometriotic lesions and makes it easier to visualize and identify them, knowing that these subtle lesions may well be the cause of the pain. However, its usefulness is decreased if performed after the initiation of surgery because of the bleeding incurred from dissection, which makes it difficult to distinguish between the red blood cells and endometriotic lesions.

CONCLUSION:

Narrowband imaging can be used as an adjunct to improve the detection of endometriosis.

 

 

Biomed Res Int. 2014;2014

Impact of medical and surgical treatment of endometriosis on the cure of endometriosis and pain.

Mettler L1Ruprai R1Alkatout I1.

 

Abstract

This endometriosis study evaluates three different treatment strategies (hormonal medication, surgical, or combined treatment) and discusses the influence of endometriosis on the cure of this disease and pain relief. Four hundred and fifty patients with genital endometriosis, aged 18-44 years, were randomly distributed to three treatment groups at the first laparoscopy. They were reevaluated at a second-look laparoscopy (D 426/10), one to two months after the three-month hormonal therapy for groups 1 and 3 and five to six months later for group 2 (surgical treatment alone). Outcome data focussed on the recurrence of symptoms and pain. The three treatment options independent of the initial endoscopic endometriosis classification (EEC) stage including deep infiltrating endometriosis (DIE) achieved an overall cure rate of 50% or higher. The highest cure rate of 60% was achieved by the combined treatment, 55% by the exclusively hormonal therapy, and 50% by the exclusively surgical treatment. An overall pregnancy rate between 55% and 65% was achieved with no significant difference in relation to the therapeutical option.

 

 

 

Womens Health (Lond). 2015 Jan;11(1):19-28.

Elagolix, a novel, orally bioavailable GnRH antagonist under investigation for the treatment of endometriosis-related pain.

Ezzati M1Carr BR.

 

Abstract

Suppression of estrogen production and reduction of menstrual blood flow are the mainstays of medical treatment of endometriosis-related pain and have been traditionally achieved by methods such as combined hormonal contraception, progestins and GnRH analogs, all with comparable efficacies, though different side-effect profiles. Elagolix is the frontrunner among an emerging class of GnRH antagonists, which unlike their peptide predecessors has a nonpeptide structure resulting in its oral bioavailability. Phase I and II clinical trials have demonstrated safety of elagolix and its efficacy in partial and reversible suppression of ovarian estrogen production resulting in improvements in endometriosis-related pain. Phase III clinical trials are currently underway and elagolix may become a valuable addition to the armamentarium of pharmacological agents to treat endometriosis-related pain.

 

 

Womens Health (Lond). 2015 Jan;11(1):35-49.

Endometriosis: a role for stem cells.

Dhesi AS1Morelli SS.

 

Abstract

Endometriosis is a complex gynecologic condition affecting 6-10% of reproductive aged women and is a major cause of chronic pain and infertility. Mechanisms of disease pathogenesis are poorly understood. Considerable evidence supports the existence of a stem cell population in the endometrium which provides a physiologic source of regenerative endometrial cells, and multiple lines of evidence now support a key role for stem cells in the pathogenesis of endometriosis. In addition, new blood vessel formation is critical for the establishment and maintenance of endometriotic implants, a process in which endothelial progenitor cells may play an integral role. These new insights into disease pathogenesis present exciting opportunities to develop targeted and more effective therapeutic options in the management of this common and challenging disease.

 

 

 

Jpn J Clin Oncol. 2015 May;45(5):405-7.

Ovarian cancer: new developments in clear cell carcinoma and hopes for targeted therapy.

Yamashita Y1.

 

Abstract

Until recently, ovarian clear cell carcinoma was recognized by its unique morphology and unfavorable patient outcome primarily due to tumor chemoresistance. Recently, specific molecular characteristics of ovarian clear cell carcinoma, such as PI3CA mutation, ARID1a mutation and MET amplification, have been elucidated. In addition, an association between endometriosis and the tumor has also been a focus of research in recent years. The aim of this review is to discuss the specificity and importance of molecular changes and various intriguing points that are not solved until today. Finally, future aspects, including hopes for the development of novel therapies, are discussed.

 

 

Hum Reprod. 2015 Apr;30(4):833-9.

Histological evaluation of ureteral involvement in women with deep infiltrating endometriosis: analysis of a large series.

Seracchioli R1Raimondo D2Di Donato N2Leonardi D2Spagnolo E2Paradisi R3Montanari G2Caprara G4Zannoni L2.

Abstract

STUDY QUESTION:

In women with deeply infiltrating endometriosis (DIE) what is the prevalence of involvement of endometriotic tissue and fibrosis in ureteral endometriosis (UE), as assessed by histological staining?

SUMMARY ANSWER:

In women with DIE, ureteral involvement is more often due to endometriotic tissue rather than fibrosis.

WHAT IS KNOWN ALREADY:

In the current literature, histological evaluation of ureteral endometriosis is mainly based on the degree of wall infiltration by endometriosis instead of the tissue composition. A few studies reported ill-defined and contradictory histological data on the tissue composition of UE.

STUDY DESIGN, SIZE, DURATION:

Retrospective observational study based on clinical records of women affected by DIE, laparoscopically treated for UE at a tertiary referral center, between January 2010 and March 2013. All cases of ureteral nodule excision or ureterectomy with histological examination of the specimens were included. Exclusion criteria were other identified causes of hydroureteronephrosis, medical therapy for a period of at least 3 months before surgery and previous surgery for DIE.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

A total of 77 patients were included in the study and among them seven (9%) presented with bilateral ureteral involvement, giving a total of 84 cases of UE available for analysis. All patients had stage IV endometriosis. According, respectively, to the presence of endometrial glands and/or stroma cells or of fibrotic tissue only, the endometriotic UE and fibrotic UE groups were compared with regard to hydroureteronephrosis at pre-operative urinary tract computerized tomography scan, type of surgical procedure performed to treat UE (nodule removal or ureterectomy), association with other locations of the disease and post-operative complications (ureteral fistula or stenosis).

MAIN RESULTS AND THE ROLE OF CHANCE:

For the 84 cases of UE, 65 (77%) and 19 (23%), respectively, showed endometriotic tissue and fibrotic tissue only. Presence of hydroureteronephrosis and endometriotic pattern of UE showed a significant association [endometriotic UE 44/65 (68%) versus fibrotic UE 8/19 (42%); P = 0.04]. Fibrotic pattern of UE and presence of concomitant recto-vaginal endometriosis showed a significant association [endometriotic group: 29/65 (45%) versus fibrotic group 18/19 (95%); P < 0.001].

LIMITATIONS, REASONS FOR CAUTION:

The retrospective and monocentric (tertiary referral center) study design.

WIDER IMPLICATIONS OF THE FINDINGS:

Besides the distinction between extrinsic and intrinsic UE based on the degree of wall infiltration by endometriosis, a new classification according to the histological pattern of UE could be useful for clinicians, both in the diagnostic and therapeutic fields.

 

 

Biol Reprod. 2015 Mar;92(3):64.

The role of the lymphatic system in endometriosis: a comprehensive review of the literature.

Jerman LF1Hey-Cunningham AJ2.

 

Abstract

Endometriosis is a benign gynecological disorder characterized by the presence of tissue resembling the endometrium in locations outside the uterus. The pathogenesis of endometriosis is still unknown; however, it is believed that the lymphatic system plays major roles in the development and progression of the disease. The lymphatic dissemination theory has been proposed to explain the presence of endometrial and/or endometriotic tissue in lymphatic vessels, lymph nodes, and rare sites, as well as high reoccurrence rates following treatment. Despite the importance of the lymphatic system in many aspects of endometriosis, there has been no previous thorough scientific update on its role in the disease. A review of scientific literature on the lymphatic system, lymphangiogenesis, and immunological changes associated with endometriosis was conducted. Lymphangiogenic potential is disturbed and lymphatic vessel density increased in the eutopic endometrium of women with endometriosis, likely promoting the entry of endometrial tissues into the lymphatic circulation. Endometriotic lesions and endometrial-like cells are present in uterine-draining nodes and various other pelvic lymph nodes. Immune responses are impaired in uterine-draining nodes, likely favoring the survival of endometrial cells and lesion establishment. In addition, lymphangiogenesis in endometriotic lesions may contribute to lesion growth and persistence, and promote the spread of endometrial cells to draining lymph nodes. The evidence reviewed in this paper supports the theory of lymphatic dissemination of endometriosis and highlights the roles of the lymphatic system in the pathogenesis and persistence of endometriosis. Understanding these roles is crucial for establishment of novel therapeutic approaches.

 

 

Gynecol Obstet Invest. 2015;79(4):229-33.

Endometriosis and perceived stress: impact of surgical and medical treatment.

Lazzeri L1Orlandini CVannuccini SPinzauti STosti CZupi ENappi REPetraglia F.

Abstract

BACKGROUND:

The aim of the study was to investigate the levels of perceived stress in a group of women with a long-term history of endometriosis in conjunction with surgical and/or medical treatments.

METHODS:

A clinical trial was conducted at the Department of Molecular and Developmental Medicine, University of Siena, in collaboration with a non-profit association of women with endometriosis, A.P.E. Onlus. Patients (n = 204) with a previous diagnosis of endometriosis (for at least 3 years) were included in this study. Each patient completed a semi-structured questionnaire and a validated scale to assess perceived stress, the Perceived Stress Scale (PSS) by e-mail.

RESULTS:

The study showed that in women with a long-term history of endometriosis, the level of perceived stress was increased by repeated surgical treatments and reduced by some medical treatments. The median PSS value was 23 (range 9-36) and 30.6% of the study population were included in the highest stress category (>26). The highest levels were found in patients who had undergone the most surgery. The use of progestins was associated with a lower perceived stress (p = 0.004) than in the patients treated with gonadotropin-releasing hormones.

CONCLUSIONS:

Long-term endometriosis has a relevant impact on perceived stress, in particular in those undergoing repeated surgery.

 

 

Scand J Gastroenterol. 2015 Mar;50(3):291-9.

Severe gastrointestinal dysmotility developed after treatment with gonadotropin-releasing hormone analogs.

Cordeddu L1Bergvall MSand ERoth BPapadaki ELi LD’Amato MOhlsson B.

Abstract

BACKGROUND:

Sporadic cases of abdominal pain and dysmotility has been described after treatment with gonadotropin-releasing hormone (GnRH) analogs. The aim of the present study was to scrutinize for patients with severe gastrointestinal complaints after treatment with GnRH analogs, to describe the expression of antibodies against progonadoliberin-2, GnRH1, GnRH receptor (GnRHR), luteinizing hormone (LH), and LH receptor in serum in these patients, and to search for possible triggers and genetic factors behind the development of this dysmotility.

METHODS:

Patients suffering from prolonged gastrointestinal complaints after treatment with GnRH analogs at the Department of Gastroenterology, Skåne University Hospital, were included. GnRHR and LH receptor (LHCGR) genes were exome-sequenced. Serum was analyzed by enzyme-linked immune sorbent assays for the presence of antibodies. Healthy blood donors and women treated with GnRH analogs because of in vitro fertilization (IVF) were used as controls.

RESULTS:

Seven patients with severe gastrointestinal complaints after GnRH treatment were identified, of whom six suffered from endometriosis. Several variants were found within the 11 exons of LHCGR. The minor allele G, at the single nucleotide polymorphism rs6755901, was detected in homozygosity in two patients (28.5%) who had developed chronic intestinal pseudo-obstruction and in 5.5% of the IVF controls. Three patients expressed IgM antibodies against progonadoliberin-2 and three against GnRH1 (42.9%) when cut off was set to a titer >97.5th percentile in blood donors.

CONCLUSION:

A high prevalence of endometriosis, polymorphism in the LHCGR and GnRH1 and progonadoliberin-2 antibodies in serum was found among the patients with severe dysmotility after treatment with GnRH analogs.

 

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