Radiol Med. 2014 May;119(5):291-7.

How to improve MRI accuracy in detecting deep infiltrating colorectal endometriosis: MRI findings vs. laparoscopy and histopathology.

Valentini AL1Gui BMiccò MMingote MCNinivaggi VGuido MZannoni GFMarrucci EBonomo L.

 

Abstract

OBJECTIVE:

To verify whether the capability of magnetic resonance imaging (MRI) in diagnosing deep infiltrating colorectal endometriosis (DICE) is improved using an association of MRI findings.

METHODS AND MATERIALS:

The imaging database of our Institute of Radiology was retrospectively reviewed to identify patients subjected to MRI for a suspicion of deep infiltrating endometriosis. Medical history was then investigated and only patients who were also subjected to laparoscopy (LA) were included. Absence of LA represented the exclusion criterion. Images were evaluated twice by two radiologists using two different diagnostic criteria for an abnormal result: the contemporary presence of nodules or hypointense plaque-like lesions in the adjacent fat plane and bowel wall thickness, without (first criterion) or with (second criterion) semicircular shape (i.e. “radial and retracting shape”). Radiologists worked in consensus evaluating images in two separate sessions, using the first criterion in the first section and the second criterion in the second one. MRI results were compared with LA or histopathology as the gold standard by 2 × 2 tables and statistically analyzed (k statistics). Likelihood-ratio test was also performed, being independent from the prevalence of the disease.

RESULTS:

By consulting case sheets, 33/50 females (ranging age 24-39 years, mean age 32.2 years) who were subjected to MRI also underwent LA. Intestinal resection for DICE was performed in 11/33 patients; in 22/33 superficial intestinal foci, adhesions/nodules in the fat plane were simply removed. When the first criterion was applied, MRI agreement with histopathology or LA was poor (51.5 %) (k value = 0.20; p < 0.055), while it was improved (96.9 %) when using the second diagnostic criterion (k value = 0.93; p < 0.0000). Likelihood ratio was 1.375 (95 % CI 0.69-2.72) using the first and 22 (95 % CI 20.08-24.1) using the second criterion.

CONCLUSION:

The second criterion, or the joint presence of nodules or hypointense plaque-like lesions in the adjacent fat plane and bowel wall thickness showing “radial and retracting shape”, improves MRI capability in DICE diagnosis. It can be considered an effective indicator of DICE on T2-weighted images at 1.5-T MRI, and can ensure the correct preoperative assessment of the disease for the best therapeutic procedure and treatment planning.

 

J Clin Diagn Res. 2013 Oct;7(10):2241-3.

Influence of endomeriotic cyst diameter and the severity of endometriosis on the ovarian parenchyma excised during laparoscopic cystectomy.

Ramachandran A1Dhulkhed SBhakta RBhat RGRao ACVasudeva AVishalakshi AKumar P.

 

Abstract

INTRODUCTION:

Endometrioma is a common form of endometriosis and it is represented by endometriotic deposits within the ovaries which accounts for upto 17-44% of cases. Laparoscopic stripping of ovarian endometriotic cysts is an accepted technique owing to low recurrence rates. Decrease in residual ovarian tissue volume was noted in many studies followed cystectomy. This study aims at estimating whether the size of endometriotic cyst is related to ovarian parenchyma excised along with cyst wall.

MATERIAL AND METHODS:

Prospective study was done at University teaching hospital for one year. A total of 56 women underwent laparoscopic endometriotic cystectomy. Cystectomy was done by stripping method and endometriosis was staged according to revised American Society of Reproductive Medicine classification (rASRM). The endometrioma wall was evaluated histologically and were categorised into 2 groups based on semi- quantitative scale of 0-4. Group 1 and 2 showed grade 0, 1, 2 and 3, 4 in the cyst wall respectively.

RESULTS:

Mean age of patients was 31.4 years, duration of infertility was 4.1 years and cyst diameter measured 6.3 cm. 73.2% (n=41) were in Group 1 and 26.8% (n=15) were in Group 2 , mean cyst diameter was being 4.3 cm and 5.0 cm respectively. There was no significant statistical correlation between preoperative cyst diameter and ovarian parenchyma removed (p=0.15). 93.3% (n=14) of group 2, and only 65.8% (n=27 ) of group 1 were found to have moderate to severe endometriosis, indicating there is correlation between disease severity and loss of ovarian tissue (p= 0.04).

CONCLUSION:

Endometriotic cystectomy when performed with accurate surgical technique leads to no significant ovarian tissue removal. However, disease severity significantly determines the loss of normal ovarian parenchyma.

 

 

 

Biomed Res Int. 2013;2013:849492.

An influence of immunomodulation on Th1 and Th2 immune response in endometriosis in an animal model.

Szymanowski K1Niepsuj-Biniaś JDera-Szymanowska AWołuń-Cholewa MYantczenko AFlorek EOpala TMurawski MWiktorowicz K.

 

Abstract

AIM:

To assess the role of the Th1 and Th2 cellular response in the etiology of endometriosis observed in a rat model, with the use of the RESAN immunomodulator.

MATERIALS AND METHODS:

A comparative analysis of cytokines in blood serum typical of Th1 (TNF-α and INF-γ ) and Th2 (IL-4, IL-6, IL-10) cell response in groups of rats, in which RESAN preparation was used as prophylaxis (Gr. I) or treatment (Gr. II) of endometriosis.

RESULTS:

The results indicated an increase in the level of cytokines in blood serum typical of Th2 cell response by comparing the second and third stages of the experiment in the second group of rats and a decrease in IL-4 and IL-10 between III and IV stages. There was a significant difference in cytokine levels during the third stage of the experiment by comparing I and II groups of rats. In the III group of rats, levels of IL-10 significantly increased between the II and III stages of the experiment.

CONCLUSION:

RESAN preparation shows Th2 cell response, inhibiting the development of endometriosis in a rat model. Due to successful prophylactic action, one may speculate that RESAN vaccine may be effective as a complementary treatment after surgical excision.

 

 

Zhonghua Yi Xue Za Zhi. 2013 Aug 6;93(29):2315-7.

Diagnostic value of magnetic resonance imaging in special-site ectopic pregnancy.

Fang BD1Chen MKYao QDXu CYYan ZH.

 

Abstract

OBJECTIVE:

To explore the magnetic resonance imaging (MRI) features and diagnostic value of special-site ectopic pregnancy.

METHODS:

The MRI features of special-site ectopic pregnancy on 39 pathologically confirmed cases were retrospectively analyzed. All cases received ultrasonic inspection, MRI plain scan and 11 cases underwent enhanced scan.

RESULTS:

In 39 cases, there were 3 cases of interstitial tubal pregnancy (n = 3), cornual pregnancy (n = 8) and uterine scar pregnancy (n = 28). The accuracy rates of location and diagnosis were 94.9% and 82.1% respectively. And they were both higher than the rates of ultrasound. They were classified into two groups by clinical outcomes:pregnancy and miscarriage. In 22 cases of pregnancy, there were sac in sac (n = 9) and complete fertilized egg (n = 13). In 17 cases of miscarriage, there were irregular honeycomb (n = 7), ring (n = 6) and mass (n = 4). Among 11 enhanced cases, there were significant enhancement (n = 4), flake or cord-like enhancement (n = 5), a little strengthen on edge (n = 1) and no enhancement (n = 1). The group had intrauterine decidual tissue hyperplasia (n = 22), ovarian cyst (n = 8), pelvic fluid (n = 6), adenomyosis (n = 3), fibroid (n = 2), endometriosis in pelvic and abdominal wall scar area (n = 1) and mild hydrops in right kidney and ureter (n = 1).

CONCLUSION:

The MRI features of special-site ectopic pregnancy are characteristic and important for clinical treatment.

 

 

Clin Nucl Med. 2014 Feb;39(2):193-5.

I SPECT/CT demonstrated ovarian endometrioma.

Chuang TL1Hsu CSWang YF.

 

Abstract

A 44-year-old woman had a history of papillary thyroid carcinoma and underwent total thyroidectomy and I ablation therapy. During the follow-up, 2-mCi I cancer workup showed an unusual shape of uptake in the pelvic region. Hybrid SPECT/CT revealed uptake posterior to the uterus, where sonography showed an 85.4-mm right ovarian endometrioma just corresponding to the location. Laparoscopic salpingo-oophorectomy showed right ovarian endometrioma (7 cm) and left ovarian cyst (4 cm). Pathologic findings showed bilateral endometriosis. After that survey, follow-up I cancer workup showed left supraclavicular, pretracheal, and right hilar metastatic lymphadenopathy with pulmonary metastasis, but no pelvic uptake was noted.

 

 

 

 

Int J Gynecol Pathol. 2014 Jan;33(1):30-4.

Fatal case of luteinized thecoma with sclerosing peritonitis in a 40-year-old woman.

Bahar B1Hu ZSzpaderska ALiotta MPotkul RKSmith DErşahin Ç.

 

Abstract

We describe the pathologic and clinical presentation of a very rare, fatal case of luteinized thecoma with sclerosing peritonitis in a 40-year-old woman, who had a history of total abdominal hysterectomy and a left salpingo-oophorectomy in 2003. The patient presented with abdominal pain, and radiologic examinations revealed a 10-cm heterogenous right pelvic mass with partial necrosis. The patient eventually underwent an exploratory laparotomy, which revealed an ovarian tumor with multiple implants in the peritoneal cavity. The ovarian lesion was made up of spindle cells among clusters of luteinized stromal cells that expanded to the ovarian cortex. Tumor cells were positive for vimentin, estrogen and progesterone receptors, and CCD68 (focally) and negative for CD34, α-smooth muscle actin, β-catenin, and desmin by immunohistochemical studies. Luteinized cells were positive for α-inhibin and calretinin. Tumor cells exhibited low Ki-67 proliferation indices. The patient died because of the sclerosing peritonitis component of the disease.

 

 

World J Clin Cases. 2013 Apr 16;1(1):34-6.

Intracystic hemorrhage in a non-endometriotic mullerian vaginal cyst.

Rivlin ME1Meeks GRGhafar MALewin JR.

 

Abstract

The commonest type of simple vaginal cyst is the Mullerian cyst. These are typically lined by columnar epithelium and contain serous or mucinous fluid. If blood is found in the cyst, the source is usually due to the presence of endometrial elements in the cyst wall. The cyst is then termed an endometriotic cyst. In this case report, we have described a woman with a symptomatic 3 cm upper vaginal cyst who underwent surgical excision of the cyst. The cyst cavity was found to be full of old dark blood and mucous, however the wall contained no endometrial tissue and was lined by columnar epithelium which stained positive for mucous with mucicarmine. No cause for the intracystic hemorrhage was identified. We conclude that intracystic hemorrhage can occur in a simple Mullerian vaginal cyst in the absence of endometrial components.

 

 

Int J Gynecol Cancer. 2014 Jan;24(1):36-42

Differences in LINE-1 methylation between endometriotic ovarian cyst and endometriosis-associated ovarian cancer.

Senthong A1Kitkumthorn NRattanatanyong PKhemapech NTriratanachart SMutirangura A.

 

Abstract

BACKGROUND:

Endometriosis in endometriosis-associated ovarian cancer (EAOC) refers to lesions that can derive from endometriotic ovarian cysts (ECs) that form in the ovarian endometrium with the potential to transform into full-blown ovarian cancer. Hypomethylation of long interspersed element-1 (LINE-1 or L1) is a common epigenomic event in several cancers and is strongly associated with ovarian cancer progression.

OBJECTIVES:

To evaluated alterations in LINE-1 methylation between EC, ovarian endometrioid adenocarcinoma (OEA), EAOC, and ovarian clear cell carcinoma (OCC).

METHODS/ MATERIALS:

First, LINE-1 methylation status in 19 normal endometrium, 29 EC, 35 OCC, and 22 OEA tissues from unrelated samples were compared. Then, specific areas of eutopic endometrium, contiguous endometriosis, and cancer arising from 16 EAOCs were collected by microdissection and analyzed for LINE-1 methylation status.

RESULTS:

The total LINE-1 methylation levels were significantly different among the endometrium, endometriosis, and ovarian cancer (P < 0.001). A stepwise decrease in LINE-1 methylation was observed in the following order: normal endometrium, EC, OEA, and OCC. Interestingly, endometriosis in EAOC of both OEA (P = 0.016) and OCC (P = 0.003) possessed a higher percentage of LINE-1 unmethylated loci than EC.

CONCLUSION:

Our data implicate that LINE-1 hypomethylation is an early molecular event involved in OEA and OCC malignant transformation. Precise measurements of LINE-1 methylation may help to distinguish EC and endometriosis in EAOC.

 

 

 

 

 

 

Ann Hum Genet. 2014 Mar;78(2):104-16.

Tumor necrosis factor and interleukin-6 gene polymorphisms and endometriosis risk in Asians: a systematic review and meta-analysis.

Li J1Chen YWei SWu HLiu CHuang QLi LHu Y.

 

Abstract

A relationship between endometriosis and tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) gene polymorphisms has been raised for Asians. However, this topic is controversial. This study was a meta-analysis to explore whether TNF-α/IL-6 gene polymorphisms were associated with a risk of endometriosis in Asians. By searching PubMed, HuGENet, and China National Knowledge Infrastructure (CNKI) databases, 17 studies were identified and included (3372 cases and 4008 controls). The odds ratio (OR) with 95% confidence interval (CI) was used to assess the association between TNF-α/IL-6 gene polymorphisms and endometriosis risk. An association of TNF-α gene -1031T/C polymorphism with endometriosis was found (TT + TC vs. CC: OR 0.50, 95% CI 0.30-0.82, I(2) = 37.1%, P = 0.20; TT vs. CC: OR 0.50, 95% CI 0.30-0.82, I(2) = 43.0%, P = 0.173; TC vs. CC: OR 0.49, 95% CI 0.29-0.83, I(2) = 10.6%, P = 0.327). In addition, TNF-α-238A/G and IL-6 -174C/G gene polymorphisms were also likely to be associated with endometriosis in Asians. For the TNF-α-238A/G gene polymorphism, the OR was 1.577 (95% CI: 1.01-2.48). For the IL-6 -174C/G gene polymorphism, the OR was 1.554 (95% CI: 1.04-2.31). No associations were detected between the TNF-α-308A/G and IL-6 -634C/G polymorphisms and susceptibility to endometriosis. Our results indicate that the TNF-α gene -1031T/C polymorphism can reduce the risk of endometriosis, but for Asians, TNF-α-238A/G and IL-6 -174C/G gene polymorphisms may be a risk factor for endometriosis. No association was found for the TNF-α-308A/G and IL-6 -634C/G gene polymorphisms.

 

 

 

Eur J Obstet Gynecol Reprod Biol. 2014 Jan;172:97-101.

Retroperitoneal and retrograde total laparoscopic hysterectomy as a standard treatment in a community hospital.

Volpi E1Bernardini L2Angeloni M2Cosma S2Mannella P2.

 

Abstract

OBJECTIVE:

To report our experience with a modified procedure for total laparoscopic hysterectomy based on a retrograde and retroperitoneal technique. This surgical approach is analyzed on a consecutive series of patients in a community hospital and theoretical educational advantages are proposed.

STUDY DESIGN:

All patients undergoing hysterectomy from January 2012 to April 2013 were included in the study. A detailed description of the technique is given. As main outcome measures we evaluated: the number and rate of patients excluded from laparoscopic approach, the rate of late complications need readmission, the rate of transfusions, the rate of conversion to laparotomy and the number of minor complications. The main concern of the study was ureteral complications.

RESULTS:

Overall 174 patients underwent hysterectomy in our unit. The rate of patients submitted to laparoscopic hysterectomy was 97.5%. The number of complications needing re-admission was three (2%). The rate of conversion was 2.7%. In the study period, two (1.2%) ureteral complications were observed (late fistulae). There were four bladder lesions but the patients were released on the same day as the patients with no lesion.

CONCLUSIONS:

Opening the retroperitoneum allows rapid control of the main uterine vessels by coagulation, and constant checks on the ureter. Difficult benign situations can be managed. Even in a non-referral center about 94% of hysterectomies can be performed by laparoscopic surgery. This approach is helpful and may be reproducible in gynecological procedures.

 

 

Mol Hum Reprod. 2014 Apr;20(4):309-17.

Differential induction of autophagy by mTOR is associated with abnormal apoptosis in ovarian endometriotic cysts.

Choi J1Jo MLee EKim HJChoi D.

 

Abstract

Mammalian target of rapamycin (mTOR) is known to be a major negative regulator of autophagy. Recent studies have shown that mTOR activity is abnormally increased in endometriotic lesions. In endometriosis, abnormal mTOR activity may contribute to the alteration of endometrial cell autophagy, which may affect apoptosis because endometrial cell autophagy is directly involved in the regulation of apoptosis. To test this hypothesis, we investigated whether endometrial cell autophagy is altered by aberrant mTOR activity and is associated with apoptosis in ovarian endometriotic cysts. Our results show that endometrial cell autophagy induction was increased by mTOR inhibition as the menstrual cycle progresses in the normal endometrium, and that it is correlated with apoptosis. However, in endometriotic tissues from ovarian endometriotic cysts, autophagy, mTOR activity and apoptosis were constant throughout the menstrual cycle, suggesting that a constant level of autophagy is maintained by disinhibition of mTOR activity during the menstrual cycle in endometriotic tissues and is related to decreased apoptosis. Indeed, compared with normal endometrium, increased mTOR activity during the secretory phase in endometriotic tissues inhibited autophagy and apoptosis induction. In addition, to determine the direct effect of autophagy induction mediated by mTOR on endometriotic cell apoptosis, endometriotic cells were treated with rapamacin (mTOR inhibitor) with and without 3-methyladenine (3-MA, autophagy inhibitor). Although rapamycin treatment induced autophagy and led to apoptosis promotion, the pro-apoptotic effect of rapamycin was reversed by the addition of 3-MA, suggesting that mTOR inhibition promotes endometriotic cell apoptosis via autophagy induction. In conclusion, our results suggest that aberrant mTOR activity in ovarian endometriotic cysts leads to alteration of endometrial cell autophagy, which is associated with abnormal apoptosis.

 

 

Int J Mol Epidemiol Genet. 2013 Nov 28;4(4):193-206.

Fine mapping of variants associated with endometriosis in the WNT4 region on chromosome 1p36.

Luong HT1Painter JNShakhbazov KChapman BHenders AKPowell JENyholt DRMontgomery GW.

 

Abstract

Genome-wide association studies show strong evidence of association with endometriosis for markers on chromosome 1p36 spanning the potential candidate genes WNT4, CDC42 and LINC00339. WNT4 is involved in development of the uterus, and the expression of CDC42 and LINC00339 are altered in women with endometriosis. We conducted fine mapping to examine the role of coding variants in WNT4 and CDC42 and determine the key SNPs with strongest evidence of association in this region. We identified rare coding variants in WNT4 and CDC42 present only in endometriosis cases. The frequencies were low and cannot account for the common signal associated with increased risk of endometriosis. Genotypes for five common SNPs in the region of chromosome 1p36 show stronger association signals when compared with rs7521902 reported in published genome scans. Of these, three SNPs rs12404660, rs3820282, and rs55938609 were located in DNA sequences with potential functional roles including overlap with transcription factor binding sites for FOXA1, FOXA2, ESR1, and ESR2. Functional studies will be required to identify the gene or genes implicated in endometriosis risk.

 

 

 

 

J Obstet Gynaecol Res. 2014 Mar;40(3):770-8.

Resveratrol suppresses inflammatory responses in endometrial stromal cells derived from endometriosis: a possible role of the sirtuin 1 pathway.

Taguchi A1Wada-Hiraike OKawana KKoga KYamashita AShirane AUrata YKozuma SOsuga YFujii T.

 

Abstract

AIM:

Endometriosis is a chronic inflammatory disease. Sirtuin 1 (SIRT1) plays a role in regulation of inflammation. The role of SIRT1 in endometriosis remains unknown. We here addressed the anti-inflammatory effects of SIRT1 on endometriosis.

METHODS:

The expression of SIRT1 in human ovarian endometriomas and eutopic endometria were examined using immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Endometriotic stromal cells (ESC) obtained from endometriomas were exposed to either resveratrol or sirtinol, an activator or inhibitor of sirtuins, respectively, and tumor necrosis factor (TNF)-α-induced interleukin (IL)-8 release from the ESC was assessed at mRNA and protein levels.

RESULTS:

Both immunochemistry and RT-PCR demonstrated that SIRT1 was expressed in ESC and normal endometrial stromal cells. Resveratrol suppressed TNF-α-induced IL-8 release from the ESC in a dose-dependent manner while sirtinol increased IL-8 release.

CONCLUSION:

These opposing effects of SIRT1-related agents suggest that IL-8 release from the ESC is modulated through the SIRT1 pathway. Resveratrol may have the potential to ameliorate local inflammation in endometriomas.

 

 

Arch Med Res. 2014 Jan;45(1):31-5.

Aberrant telomerase expression in the endometrium of infertile women with deep endometriosis.

Mafra FA1Christofolini DM1Cavalcanti V1Vilarino FL1André GM1Kato P2Bianco B3Barbosa CP1.

 

Abstract

BACKGROUND AND AIMS:

Considering the complex cellular and molecular mechanisms involved in endometriosis formation and progression and the similarities concerning the association of endometriosis with tumorigenesis and metastasis, we hypothesized a possible relationship between telomerase and the development/progression of endometriosis. The present study aimed to evaluate the expression of telomerase in the endometrium and peritoneal endometriotic lesions from women with endometriosis and controls.

METHODS:

A case-control study was performed comprising 25 infertile women with endometriosis and 44 fertile women without endometriosis as controls. Samples of endometrium and endometriotic peritoneal lesions of the same patient were harvested in the late luteal phase of the cycle. The expression of hTERT and GAPDH genes was measured by mRNA using qRT-PCR based on TaqMan methodology. Student t test was used to compare the values between the groups; p >0.05 was accepted as statistically significant.

RESULTS:

The mean expression of hTERT in the endometriosis group was significantly high when compared to the control group (1.24 ± 4.67 vs. 0.31 ± 1.10, p = 0.026). When the expression of hTERT was compared in relation to disease stage, the group of moderate/severe endometriosis showed increased expression in relation to control group (2.59 ± 7.35 vs. 0.31 ± 1.10, p = 0.026). Regarding endometriotic peritoneal lesions, only one 1/25 expressed hTERT mRNA. This patient had deep endometriosis.

CONCLUSIONS:

There was an association between the expression of telomerase (hTERT mRNA) and the genesis and progression of endometriosis.

 

 

PLoS One. 2013 Dec 4;8(12):e82512.

L1 cell adhesion molecule as a potential therapeutic target in murine models of endometriosis using a monoclonal antibody approach.

Silveira CG1Finas DHunold PKöster FStroschein KCanny GOMoldenhauer GAltevogt PRody AHornung D.

 

Abstract

BACKGROUND/AIMS:

The neural cell adhesion molecule L1CAM is a transmembrane glycoprotein abnormally expressed in tumors and previously associated with cell proliferation, adhesion and invasion, as well as neurite outgrowth in endometriosis. Being an attractive target molecule for antibody-based therapy, the present study assessed the ability of the monoclonal anti-L1 antibody (anti-L1 mAb) to impair the development of endometriotic lesions in vivo and endometriosis-associated nerve fiber growth.

METHODS AND RESULTS:

Endometriosis was experimentally induced in sexually mature B6C3F1 (n=34) and CD-1 nude (n=21) mice by autologous and heterologous transplantation, respectively, of endometrial fragments into the peritoneal cavity. Transplantation was confirmed four weeks post-surgery by in vivo magnetic resonance imaging and laparotomy, respectively. Mice were then intraperitoneally injected with anti-L1 mAb or an IgG isotype control antibody twice weekly, over a period of four weeks. Upon treatment completion, mice were sacrificed and endometrial implants were excised, measured and fixed. Endometriosis was histologically confirmed and L1CAM was detected by immunohistochemistry. Endometriotic lesion size was significantly reduced in anti-L1-treated B6C3F1 and CD-1 nude mice compared to mice treated with control antibody (P<0.05). Accordingly, a decreased number of PCNA positive epithelial and stromal cells was detected in autologously and heterologously induced endometriotic lesions exposed to anti-L1 mAb treatment. Anti-L1-treated mice also presented a diminished number of intraperitoneal adhesions at implantation sites compared with controls. Furthermore, a double-blind counting of anti-neurofilament L stained nerves revealed significantly reduced nerve density within peritoneal lesions in anti-L1 treated B6C3F1 mice (P=0.0039).

CONCLUSIONS:

Local anti-L1 mAb treatment suppressed endometriosis growth in B6C3F1 and CD-1 nude mice and exerted a potent anti-neurogenic effect on induced endometriotic lesions in vivo. The findings of this preliminary study in mice provide a strong basis for further testing in in vivo models.

 

 

Springerplus. 2013 Nov 20;2:618.

Therapeutic effect of dienogest on adenosarcoma arising from endometriosis: a case report.

Tasaka N1Matsumoto KSatoh TMinaguchi TOnuki MOchi HTanaka YOSakata ANoguchi MYoshikawa H.

 

Abstract

Dienogest is a novel synthesized progestin used for treatment of endometriosis. This is the first case report describing a therapeutic effect of dienogest on a gynecologic malignancy. The patient was a 44-year-old woman with advanced adenosarcoma arising from the endometriosis in the rectovaginal space and infiltrating the left pelvic wall, left ureter, rectum and vagina. The residual tumor after tumor debulking surgery was resistant to both chemotherapy and radiotherapy. Dienogest was used as a substitute for medroxyprogesterone acetate because of the presence of deep vein thrombosis. Based on the RECIST criteria, partial response was obtained with oral dienogest therapy at six months and the serum CA125 level also decreased from 70 U/ml to 16 U/ml. The tumor remained stable up to 21 months. Thromboembolism or other adverse effects did not occur during the dienogest therapy. Dienogest may be useful for the treatment of adenosarcoma arising from endometriosis.

 

 

J Ovarian Res. 2013 Dec 11;6(1):90.

Peritoneal full-conditioning reduces postoperative adhesions and pain: a randomised controlled trial in deep endometriosis surgery.

Koninckx PR1Corona RTimmerman DVerguts JAdamyan L.

 

Abstract

BACKGROUND:

To translate the concept of full-conditioning (FC) from animal experiments to the human, and to evaluate the efficacy for adhesion prevention. FC consisted of decreasing acute inflammation by 86% CO2+ 10% N2O + 4% O2 for the pneumoperitoneum, cooling of the peritoneal cavity, humidification, heparinized rinsing solution and 5 mg of dexamethasone as demonstrated in animal models.

METHODS:

A randomized controlled trial (RCT: NCT01344486) comparing standard laparoscopy with full conditioning together with a barrier in a 2/3 ratio in 44 women undergoing deep endometriosis surgery at KULeuven. The primary aim was reduction of adhesions. Secondary aims were CO2 resorption, postoperative pain and recovery. Randomization was performed after signing informed consent. Adhesion scoring during second look laparoscopy and pain scoring were done blindly.

RESULTS:

In the FC group (n = 16) adhesions were completely prevented in 12/16 women whereas in the control group (n = 11) all women had severe adhesions (P < 0.0005). Also the area, density and severity of adhesions were less. (P <0.001). In the control group, severity, density and area of adhesions were strongly interrelated (P = 0.0001 for all areas) suggesting a common enhancing factor. In the FC group CO2 resorption (P < 0.001), postoperative pain (P < 0.001), and CRP concentrations (P < 0.01) were lower while clinical recovery was faster (P < 0.0001) and time to first flatus (P < 0.002) shorter.

IN CONCLUSION:

This translational research confirms in the human the efficacy of FC in reducing CO2 resorption and adhesions with in addition less postoperative pain, lower postoperative CRP concentrations and an accelerated recovery.

 

 

Am J Pathol. 2014 Feb;184(2):464-71.

Serum level of IL-10 is increased in patients with endometriosis, and IL-10 promotes the growth of lesions in a murine model.

Suen JL1Chang Y2Chiu PR3Hsieh TH4Hsi E5Chen YC2Chen YF3Tsai EM6.

 

Abstract

Immune dysregulation may be involved in the development of endometriosis. The anti-inflammatory cytokine IL-10 plays an important role in eliminating unwanted cells and cellular debris in a silent way. We investigated the modulatory role of IL-10 in the development of endometriosis. We observed that the serum level of IL-10 in patients with endometriosis was significantly higher than that in healthy subjects or in control subjects with other gynecological disease. Monocyte-derived dendritic cells acquired from male donors and subsequently conditioned with serum from women with endometriosis exhibited a tolerogenic phenotype, including increased IL-10 production, lower IL-12 secretion, and down-regulation of CD86 and HLA-DR molecules. Depletion of IL-10 activity in a C57BL/6 mouse model of surgically induced endometriosis significantly decreased the size of endometrial lesions. In contrast, IL-10 administration promoted the growth of endometrial lesions in this model. In addition, infiltrated plasmacytoid dendritic cells were the primary IL-10-secreting immune cells in endometrial lesions. Our findings suggest that IL-10 may suppress immunity against endometrial implants, contributing to development of endometriosis.

 

 

Obstet Gynecol Sci. 2013 Mar;56(2):67-75.

Clinical applications of levonorgestrel-releasing intrauterine system to gynecologic diseases.

Kim ML1Seong SJ.

 

Abstract

The levonorgestrel-releasing intrauterine system (LNG-IUS), originally designed for contraception, has since been applied to various gynecologic diseases. This article summarizes the current status of clinical applications of LNG-IUS to the treatment of gynecologic diseases such as heavy menstrual bleeding, endometriosis, leiomyoma, adenomyosis, endometrial hyperplasia, and early-stage endometrial cancer.

 

 

 

 

Obstet Gynecol Sci. 2013 Mar;56(2):102-9.

Expression of CD44 in endometrial stromal cells from women with and without endometriosis and its effect on the adherence to peritoneal mesothelial cells.

Koo YH1Na YJAhn MYJeon HNYeom JILee KS.

 

Abstract

OBJECTIVE:

This study was performed to compare the expression of CD44 in endometrial stromal cells (ESCs) of women with and without endometriosis and to evaluate the role of CD44 in the adherence of ESCs to peritoneal mesothelial cells (PMCs).

METHODS:

A PMC adherence assay was performed to evaluate the adherence of ESCs to PMCs in women with and without endometriosis. The expression of CD44 mRNA was measured by reverse transcription-polymerase chain reaction. CD44 protein was evaluated by Western blot analysis.

RESULTS:

There were no significant differences in the expression of CD44 mRNA and protein in ESCs or in the binding of ESCs to PMCs between patients with endometriosis and controls. Although the expression of CD44 protein was decreased in both women with endometriosis and controls after anti-CD44 antibody treatment, there was no effect on binding of ESCs to PMCs. Treatment of ESCs with peritoneal fluid from endometriosis patients resulted in a significant increase in binding of ESCs to PMCs compared to untreated ESCs in the endometriosisgroup.

CONCLUSION:

This study demonstrates that the expression of CD44 protein in ESCs from women with endometriosis might not be directly associated with adherence to PMCs.

 

 

Obstet Gynecol Sci. 2013 Jul;56(4):234-41

Clinical efficacy of serum human epididymis protein 4 as a diagnostic biomarker of ovarian cancer: A pilot study.

Chung SH1Lee SYJu WKim SC.

 

Abstract

OBJECTIVE:

To compare accuracy of serum human epididymis protein 4 (HE4) levels with cancer antigen 125 (CA-125) levels as biomarkers for ovarian cancer.

METHODS:

The study population included 94 Korean women, including 32 patients with a diagnosis of ovarian cancer and 62 patients with a diagnosis of benign ovarian tumor. All diagnoses were confirmed by histopathological analysis. Serum HE4 levels were assessed using an HE4 enzyme immunoassay, which were performed according to the manufacturer’s instructions. Serum CA-125 levels were determined using a Modular analytics E170 module.

RESULTS:

The median serum CA-125 and HE4 levels were significantly higher in patients with ovarian cancer than those with other benign tumors (CA-125, 394.1 U/mL vs. 22.7 U/mL; HE4, 56.7 pM vs. 18.5 pM; P < 0.05 in both). An additional comparison revealed that the patients with endometriosis had greater median serum CA-125 levels than those with other benign ovarian tumors (32.0 U/mL vs. 17.9 U/mL, P = 0.03). Conversely, the median serum HE4 levels were similar among the two benign ovarian tumor groups, with no statistically significant difference observed (19.0 pM vs. 18.2 pM, P = 0.49). The receiver operating characteristics curve analysis for the benign ovarian tumor and ovarian cancer patients showed that HE4 showed a greater area under the curve with borderline significance when compared with CA-125 in both groups (0.93 vs. 0.85).

CONCLUSION:

Serum HE4 levels may not only allow for the detection of ovarian cancer, but also allow for better differentiation of cases of ovarian cancer versus other benign ovarian tumors compared with serum CA-125.

 

 

Obstet Gynecol Sci. 2013 Jul;56(4):256-60

Association of nursing-documented ambulation with length of stay following total laparoscopic hysterectomy for benign gynecologic disease.

Kim K1Yoo SYang EJNo JHHwang HKim YB.

 

Abstract

OBJECTIVE:

The objective was to examine the association of postoperative physical activity with length of stay in patients who received total laparoscopic hysterectomy for benign gynecologic disease.

METHODS:

The case group was composed of 70 patients who entered a critical pathway for elective total laparoscopic hysterectomy from 2009 to 2012 and were discharged behind schedule. The control group was selected from patients who were discharged on schedule, and matched to cases using 1:3 ratio propensity score matching. We compared the number of nursing-documented ambulation of the case group with that of control group.

RESULTS:

Year of surgery, age, body mass index, endometriosis, systemic disease, previous abdominal surgery and current medication were well balanced between case and control groups. The number of patients with nursing-documented ambulation in case group (19%) was not different from that in control group (11%).

CONCLUSION:

Postoperative physical activity measured by nursing-documented ambulation was not associated with length of stay in patients who underwent an elective total laparoscopic hysterectomy for benign gynecologic diseases.

 

 

Reprod Biol Endocrinol. 2013 Dec 11;11:112.

Endometriosis fertility index score maybe more accurate for predicting the outcomes of in vitro fertilisation than r-AFS classification in women with endometriosis.

Wang W1Li RFang THuang LOuyang NWang LZhang QYang D.

 

Abstract

BACKGROUND:

Endometriosis is a common disease. The most widely used staging system of endometriosis is the revised American Fertility Society classification (r-AFS classification) which has limited predictive ability for pregnancy after surgery. The endometriosis fertility index (EFI) is used to predict fecundity after endometriosissurgery. This diagnostic accuracy study was designed to compare the predictive value of the EFI with that of the r-AFS classification for IVF outcomes in patients with endometriosis.

METHODS:

199 women with endometriosis receiving IVF treatment after surgery were analysis. The EFI score and r-AFS classification in their ability to predict these IVF outcomes were compared in the same population. ROC curves were used to analyse the predictive values of the EFI and r-AFS indices for clinical pregnancy, and their accuracies were evaluated by sensitivity, specificity, and the Youden’s index.

RESULTS:

The Area Under the Curve (AUC) of the EFI score (AUC = 0.641, Standard Error(SE) = 0.039, P = 0.001, 95% CI = 0.564-0.717, cut-off score = 6) was significantly larger than that of the r-AFS classification (AUC = 0.445, SE = 0.041, P = 0.184, and 95% CI = 0.364-0.526). The antral follicle count, oestradiol level on day of hCG, number of oocytes retrieved, number of oocytes fertilised, and number of cleaved embryos in the greater than or equal to 6 EFI score group was greater than that of the lower than or equal to 5 EFI score group, and the dose of gonadotropin of the greater than or equal to 6 EFI score group were less than that in the lower than or equal to 5 EFI score group. Implantation rate, clinical pregnancy rate, and cumulative pregnancy rate in the greater than or equal to 6 EFI score group were higher than in the lower than or equal to 5 EFI score group.

CONCLUSIONS:

It suggests that the EFI has more predictive power for IVF outcomes in endometriosis patients than the r-AFS classification. The clinical pregnancy rate was higher in patients with EFI greater than or equal to 6 score than with EFI lower than or equal to 5 score.

 

 

Clin Radiol. 2014 Mar;69(3):323-30.

Thoracic endometriosis syndrome: CT and MRI features.

Rousset P1Rousset-Jablonski C2Alifano M3Mansuet-Lupo A4Buy JN5Revel MP5.

 

Abstract

Thoracic endometriosis is considered to be rare, but is the most frequent form of extra-abdominopelvic endometriosis. Thoracic endometriosis syndrome affects women of reproductive age. Diagnosis is mainly based on clinical findings, which can include catamenial pneumothorax and haemothorax, non-catamenial endometriosis-related pneumothorax, catamenial haemoptysis, lung nodules, and isolated catamenial chest pain. Symptoms are typically cyclical and recurrent, with a right-sided predominance. Computed tomography (CT) is the first-line imaging method, but is poorly specific; therefore, its main role is to rule out other pulmonary diseases. However, in women with a typical clinical history, some key CT findings may help to confirm this often under-diagnosed syndrome. MRI can also assist with the diagnosis, by showing signal changes typical of haemorrhage within diaphragmatic or pleural lesions.

 

 

 

 

Zhonghua Fu Chan Ke Za Zhi. 2013 Sep;48(9):663-6.

Clinical study of 67 cases of endometriosis coexisting with genital tract anomalies.

Wang S1Lang JH2Zhu L1.

 

Abstract

OBJECTIVE:

To investigate the pathogenesis of endometriosis by studying endometriosis coexisting with variable genital tract anomalies and analysis the association between obstructive or non-obstructive anomalies with endometriosis.

METHODS:

From January 2000 to April 2010, a total of 67 cases of endometriosis coexisting with genital tract anomalies undergoing treatment in Peking Union Medical College Hospital were studied retrospectively.

RESULTS:

According to subtypes of concurrent genital tract anomalies, 67 cases were divided into 19 cases in obstructive group and 48 cases in non-obstructive group.(1) Age and symptoms:the mean age were (22 ± 8) years in obstructive group and (32 ± 7) years in non-obstructive group, which reached statistical difference (P < 0.05). The major symptoms were dysmenorrheal or chronic pelvic pain (14/19) and amenorrhea (8/19) in obstructive group.However, in non-obstructive group, the major symptoms were dysmenorrheal or chronic pelvic pain (31%, 15/48) and infertility (35%, 17/48) and abortion (21%, 10/48).(2) Degree and incidence of endometriosis:the moderate or severe endometriosis was 11/19 in obstructive group and 40% (19/48) in non-obstructive group, which did not show statistical difference (P > 0.05). The incidence of peritoneal endometriosis, ovarian endometriosis, adenomyosis did not show significant difference between two groups (all P > 0.05). The rate of moderate or severe endometriosis coexisting with duplex uterus, uterus bicornis and uterus septus did not show significant difference in non-obstructive group (P > 0.05).

CONCLUSIONS:

The severity of endometriosis showed no association with obstructive anomalies. The results implied that there might be other factors involved in pathogenesis of endometriosis.

 

 

 

 

 

Eur J Pharmacol. 2014 Jan 15;723:167-74.

Suppression of the hypothalamic-pituitary-gonadal axis by TAK-385 (relugolix), a novel, investigational, orally active, small molecule gonadotropin-releasing hormone (GnRH) antagonist: studies in human GnRH receptor knock-in mice.

Nakata D1Masaki T1Tanaka A1Yoshimatsu M1Akinaga Y1Asada M1Sasada R1Takeyama M1Miwa K2Watanabe T3Kusaka M2.

 

Abstract

TAK-385 (relugolix) is a novel, non-peptide, orally active gonadotropin-releasing hormone (GnRH) antagonist, which builds on previous work with non-peptide GnRH antagonist TAK-013. TAK-385 possesses higher affinity and more potent antagonistic activity for human and monkey GnRH receptors compared with TAK-013. Both TAK-385 and TAK-013 have low affinity for the rat GnRH receptor, making them difficult to evaluate in rodent models. Here we report the human GnRH receptor knock-in mouse as a humanized model to investigate pharmacological properties of these compounds on gonadal function. Twice-daily oral administration of TAK-013 (10mg/kg) for 4 weeks decreased the weights of testes and ventral prostate in male knock-in mice but not in male wild-type mice, demonstrating the validity of this model to evaluate antagonists for the human GnRH receptor. The same dose of TAK-385 also reduced the prostate weight to castrate levels in male knock-in mice. In female knock-in mice, twice-daily oral administration of TAK-385 (100mg/kg) induced constant diestrous phases within the first week, decreased the uterus weight to ovariectomized levels and downregulated GnRH receptor mRNA in the pituitary after 4 weeks. Gonadal function of TAK-385-treated knock-in mice began to recover after 5 days and almost completely recovered within 14 days after drug withdrawal in both sexes. Our findings demonstrate that TAK-385 acts as an antagonist for human GnRH receptor in vivo and daily oral administration potently, continuously and reversibly suppresses the hypothalamic-pituitary-gonadal axis. TAK-385 may provide useful therapeutic interventions in hormone-dependent diseases including endometriosis, uterine fibroids and prostate cancer.

 

J Minim Invasive Gynecol. 2014 Jul-Aug;21(4):576-9.

Validity of intraoperative diagnosis at laparoscopic surgery for ovarian tumors.

Takemoto S1Ushijima K2Kawano R2Fukui A2Terada A2Fujimoto T2Imaishi H2Kamura T2.

 

Abstract

STUDY OBJECTIVE:

To evaluate the accuracy and usefulness of intraoperative diagnosis of ovarian tumor during laparoscopic surgery.

DESIGN:

Retrospective cohort study (Canadian Task Force classification II-3).

SETTING:

Tertiary care university hospital.

PATIENTS:

We reviewed the cases of 262 patients who underwent laparoscopic surgery at our institution between January 2005 and December 2011 in whom a benign ovarian tumor was diagnosed intraoperatively.

INTERVENTIONS:

Intraoperative pathologic assessment of frozen sections.

MEASUREMENTS AND MAIN RESULTS:

Intraoperative diagnosis of ovarian tumors demonstrated sensitivity of 80%, specificity of 99.6%, positive predictive value of 80%, and diagnostic accuracy of 99.2%. Mucinous tumors diagnosed intraoperatively showed differing intraoperative and final pathologic diagnoses significantly more frequently than did other types of tumors.

CONCLUSION:

Intraoperative pathologic assessment of benign ovarian tumors during laparoscopic surgery is reliable. However, clinicians should recognize that it is possible to make an incorrect diagnosis in some situations and should exercise caution accordingly.

 

 

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2013 Dec;56(12):1628-32.

Infertility in women: latest developments.

Strowitzki T1.

 

Abstract

BACKGROUND:

The incidence of female infertility has not changed since the early 1990s. Based on new data from basic research on infertility, novel options in the diagnostics and treatment of infertility have emerged, besides in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).

AIM:

This review summarizes the current knowledge on female infertility and on modern concepts in diagnostics and treatment.

METHODS:

A literature research on the causes of infertility and on treatment options was performed, including demographic factors, infectiology, anatomy, endocrinology and metabolism, endometriosis, lifestyle and environmental factors, and psychological factors.

RESULTS:

Chlamydial infection is still the major cause of tubal infertility. Improvement of the patient’s fertility by correction of endocrine and metabolic disorders, in particular thyroid dysfunction and glucose metabolism, as well as fertility surgery are of main interest.

CONCLUSIONS:

Besides assisted reproductive techniques, concepts to optimize individual fertility have gained increasing importance.

 

 

Arch Gynecol Obstet. 2014 Apr;289(4):915-20.

Polypoid endometriosis of the cervix: a case report and review of the literature.

Jaiman S1Gundabattula SRPochiraju MSangireddy JR.

 

Abstract

BACKGROUND:

Giant and multilobular endocervical polyps are rare and need to be differentiated from cervical neoplastic lesions.

CASE REPORT:

The authors report a 29-year-old sexually inactive woman presenting with a prolapsed giant endocervical polyp, associated with malodorous discharge and menorrhagia. The wide-based polyp originated in part from the posterior lip of the exocervix and in part from the endocervix. This trilobular pedunculated mass (90 × 50 × 35 mm) had small cysts on the surface and focal areas of haemorrhage. Microscopic examination revealed areas with classic endocervical mucosal polyp histology intimately mixed with expanses of endometrial stroma and occasional endometrial glands. Immunohistochemically the endometrial stroma showed strong CD10 positivity, glands were oestrogen and progesterone receptor positive and Ki-67 proliferation index was low.

CONCLUSION:

Polypoid endometriosis of the cervix is a distinct form of endometriosis that may be mistaken for a neoplasm. Five earlier reports of this entity have not described a prolapsed polyp assuming gigantic proportions. We conclude that this condition be considered in the differential diagnosis of polypoid lesions of the cervix.

 

 

 

 

J Pathol. 2014 Mar;232(4):473-81.

Frequent somatic mutations of the telomerase reverse transcriptase promoter in ovarian clear cell carcinoma but not in other major types of gynaecological malignancy.

Wu RC1Ayhan AMaeda DKim KRClarke BAShaw PChui MHRosen BShih IeMWang TL.

 

Abstract

Up-regulated expression of telomerase reverse transcriptase (TERT) and subsequent maintenance of telomere length are essential in tumour development. Recent studies have implicated somatic gain-of-function mutations at the TERT promoter as one of the mechanisms that promote transcriptional activation of TERT; however, it remains unclear whether this genetic abnormality is prevalent in gynaecological neoplasms. We performed mutational analysis in a total of 525 gynaecological cancers, and correlated TERT promoter mutations with clinicopathological features. With the exception of ovarian clear cell carcinomas, in which mutations were found in 37 (15.9%) of 233 cases, the majority of gynaecological malignancies were wild-type. TERT promoter mutation does not appear to be an early event during oncogenesis, as it was not detected in the contiguous endometriosis associated with ovarian clear cell carcinoma. Ovarian clear cell carcinoma cell lines with TERT promoter mutations exhibited higher TERT mRNA expression than those with wild-type sequences (p = 0.0238). TERT promoter mutation tended to be mutually exclusive with loss of ARID1A protein expression (p = 4.4 × 10(-9) ) and PIK3CA mutation (p = 0.0019) in ovarian clear cell carcinomas. No associations with disease-specific survival were observed for ovarian clear cell carcinoma. The above results, in conjunction with our previous report showing longer telomeres in ovarian clear cell carcinomas relative to other types of ovarian cancer, suggests that aberrations in telomere biology may play an important role in the pathogenesis of ovarian clear cell carcinoma.

 

 

Phytother Res. 2014 Jul;28(7):961-75.

Puerarin: a review of pharmacological effects.

Zhou YX1Zhang HPeng C.

 

Abstract

Puerarin is the major bioactive ingredient isolated from the root of the Pueraria lobata (Willd.) Ohwi, which is well known as Gegen (Chinese name) in traditional Chinese medicine. As the most abundant secondary metabolite, puerarin was isolated from Gegen in the late 1950s. Since then, its pharmacological properties have been extensively investigated. It is available in common foods and is used in alternative medicine. It has been widely used in the treatment of cardiovascular and cerebrovascular diseases, diabetes and diabetic complications, osteonecrosis, Parkinson’s disease, Alzheimer’s disease, endometriosis, and cancer. The beneficial effects of puerarin on the various medicinal purposes may be due to its wide spectrum of pharmacological properties such as vasodilation, cardioprotection, neuroprotection, antioxidant, anticancer, antiinflammation, alleviating pain, promoting bone formation, inhibiting alcohol intake, and attenuating insulin resistance. However, the direct molecular mechanisms and targets remain unclear. This review provides a comprehensive summary of the pharmacological effects of puerarin.

 

 

PLoS One. 2013 Dec 5;8(12):e80630.

BMPR1B up-regulation via a miRNA binding site variation defines endometriosis susceptibility and CA125 levels.

Chang CY1Chen YLai MTChang HWCheng JChan CChen CMLee SCLin YJWan LTsai PWYang SHChung CSheu JJTsai FJ.

 

Abstract

BACKGROUND:

Bone morphogenetic protein receptor I B (BMPR1B) is a transmembrane receptor mediating TGF-β signal transduction. Recent studies indicate a tumor suppressor role for BMPR1B in ovarian cancer. Polymorphism at BMPR1B 3’UTR within the miR-125b binding site alters its binding affinity toward the miRNA, which may result in insufficient post-transcriptional repression.

METHODS:

Single-nucleotide polymorphisms rs1970801, rs1434536, and rs11097457 near the miR-125b binding site in BMPR1B were genotyped by Taqman assay on 193 endometriosis patients and 202 healthy controls. BMPR1B and CA125 levels in ectopic endometrial tissues were evaluated by quantitative PCR and immunohistochemistry. Luciferase reporter assay was utilized to verify regulatory roles of BMPR1B 3’UTR with allelic variants of rs1434536 in a cell line model. Cell proliferation and migration were recorded, while expression of BMPR1B, CA125, glucocorticoid receptor (GCCR) and IL-1β were measured by quantitative PCR in endometrial cells transfected with wild-type or mutated miR-125b.

RESULTS:

This study found two endometriosis-associated SNPs, rs1434536 (P = 0.010) and rs1970801 (P = 0.0087), located within and next to a miR-125b binding site on BMPR1B. Interestingly, patients with homozygous variant alleles at rs1434536 showed significantly lower serum CA125 levels. Immunohistochemistry staining further confirmed inverse correlation between BMPR1B and CA125 levels in three rs1434536 genotypes. Cell assays demonstrated the variant allele of rs1434536 up-regulating BMPR1B at both mRNA and protein levels, which negatively correlated with CA125 and IL-1β levels. Disruption of the binding between miR-125b and BMPR1B hampered abnormal cell proliferation.

CONCLUSIONS:

SNPs of BMPR1B within and next to the miR-125b binding site manifested strong correlation with endometriosis development in a Taiwanese cohort. Disrupting the binding of miR-125b toward BMPR1B would increase protein expression, diminishing abnormal cell proliferation as well as serum and cellular CA125 levels. Genetic variation at the miR-125b binding site may play functional roles to protect against endometriosisprogression.

 

 

Vestn Ross Akad Med Nauk. 2013;(8):14-9.

Role of the genetic factors, detoxication systems and oxidative stress in the pathogenesis of endometriosis and infertility.

Dubinskaia EDGasparov ASFedorova TALapteva NV.

 

Abstract

The aim of this paper is to provide a systematic review of the role of the genetic factors, detoxication systems and oxidative stress in the pathogenesis of endometriosis and infertility. Endometriosis and infertility are still both the most uncommon diseases in gynecology. Many aspects of female reproductive function are strongly influenced by genetic factors, and numerous studies have attempted to identify susceptibility genes for disorders affecting female fertility such as polycystic ovary syndrome, endometriosis, fibroids, cancer (ovarian, vulvar, cervical), premature ovarian failure, recurrent pregnancy loss and pre-eclampsia. The most solid evidence linking specific polymorphisms to endometriosis is showed by the studies investigating a phase II detoxification enzyme. No data were found concerning influences of the genetic factors on the female infertility. Contrary, a lot of studies devoted to the genetic factors of male infertility are presented. It’s known that endometriosisassociated with increased systemic oxidative stress. The implication of increased systemic oxidative stress in disease progression or the association with other oxidative stress-related pathologic conditions needs to be addressed in further studies. The majority of studies suggest a reduced antioxidant capacity in infertile wome with endometriosis. In the present review we discussed the role of the genetic factors in the pathogenesis of endometriosis and infertility. NAT2 polimorphism, xenobiotic methabolism and exogenous factors are somehow related with these diseases. An altered balance between pro-oxidant antioxidant activities may have an impact on folliculogenesis and adequate embryo development.

 

 

 

 

 

Int J Epidemiol. 2014 Feb;43(1):255-63.

Pigmentary traits, family history of melanoma and the risk of endometriosis: a cohort study of US women.

Kvaskoff MHan JQureshi AAMissmer SA.

 

Abstract

BACKGROUND:

Endometriosis has been associated with a higher risk of cutaneous melanoma, but the mechanisms underlying this association are unknown.Some constitutional factors known to influence melanoma risk have been associated with endometriosis in some retrospective studies. However, prospective data are scarce, and more research is needed to confirm this potentially novel endometriosis risk profile.

METHODS:

To investigate the relationships between pigmentary traits, family history of melanoma and endometriosis risk, we analysed data from the Nurses’ Health Study II, a cohort of 116 430 female US nurses aged 25–42 years at inclusion in 1989. Data were collected every 2 years with 20 years of follow-up for these analyses. We used Cox proportional hazards regression models to compute relative risks(RRs) and 95% confidence intervals (CIs).

RESULTS:

During 1 212 499 woman-years of follow-up, 4763 cases of laparoscopically-confirmed endometriosis were reported among premenopausal Caucasian women. Endometriosis risk was increased with presence of naevi on the lower legs (RR=1.08, 95% CI=1.021.14) and higher level of skin’s burning reaction to sun exposure in childhood/adolescence (‘burn with blisters’: RR=1.20,95% CI=1.061.36) compared with ‘practically none’;P(trend)=0.0006) and family history of melanoma (RR=1.13, 95%CI=1.011.26).

CONCLUSION:

This assessment reports modest associations between several pigmentary traits, family history of melanoma and endometriosis risk,corroborating the results from previous retrospective studies. Our findings call for further research to better understand the mechanisms under lying these associations.

 

 

Adv Perit Dial. 2013;29:69-72.

Hemoperitoneum in a peritoneal dialysis patient from a retroperitoneal source.

Balsera C1Guest S2.

 

Abstract

Hemoperitoneum in peritoneal dialysis patients is a known but infrequent complication. Hemoperitoneum is more frequent in women because of its association with a variety of gynecologic presentations such as reflux menstruation, ovulation, endometrial tissue implants within the peritoneal cavity (endometriosis), and bleeding follicular cysts. Other intraperitoneal causes of hemoperitoneum include minor catheter or abdominal trauma, vascular anomalies, or hepatic or splenic cysts. Less frequently encountered is a presentation of hemoperitoneum from a retroperitoneal source. These presentations result either from peritoneal inflammation and subsequent peritoneal bleeding or retroperitoneal cavity pathology rupturing into the peritoneal cavity. Here, we present the case of a peritoneal dialysis patient presenting with hemoperitoneum several days after undergoing cardiac catheterization. The catheterization was complicated by a large retroperitoneal hematoma. Details of the case are reported, and other retroperitoneal causes of hemoperitoneum are reviewed.

 

 

Chin J Nat Med. 2013 Nov;11(6):666-72.

Beneficial effects of the Chinese herbal medicine Sanjie Zhentong Capsule on experimental endometriosis in rats.

Zou J1Guan Z1Zhang WY1Xiao W2Li YL3.

 

Abstract

AIM:

To analyze the composition of the Chinese herbal medicine Sanjie Zhentong Capsule (SJZTC) and test the therapeutic efficacy of each component in a rat model of endometriosis.

METHODS:

A rapid resolution liquid chromatography (RRLC) method coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (Q-TOF MS) has been developed for the analysis of SJZTC. Two main ingredients, Drac(h)onis sanguis and saponin, were tested in the endometriosis model. Sixty Lewis female rats were in the estrous cycle stage when endometriosis was experimentally initiated by peritoneal implantation of endometrial tissue. Four weeks later, a second laparotomy was performed and implant volumes were measured. After that, the implanted rats were randomized into five study groups: control group (treatment with saline), anastrozole group (treatment with anastrole, 18 μg per day), loureirin A group (treated with loureirin A, 97.2 mg), ginsenoside Re group (treated with ginsenoside Re, 64.8 mg), and SJZTC groups (treated with SJZTC, 86.4 mg) administered once a day for 4 weeks via gastric gavage. After four weeks of treatment, a third laparotomy was performed, implant volumes were re-measured, and the levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-α) were tested.

RESULTS:

A total of 38 compounds including, both the target and unknown compounds, were rapidly predicted in the capsule extract by the developed method. Compared with the control group, the anastrozole group, loureirin A group, ginsenoside Re group, and SJZTC treated group showed smaller implant volumes, as well as lower levels of VEGF and TNF-α in the peritoneal focus (P < 0.01 for all comparisons). Furthermore, parameters in the groups treated with SJZTC, loureirin A and ginsenoside Re were significantly better than the control group and the anastrozole group. These results indicate that SJZTC and its two main components are effective in reducing the development of endometriosis.

 

 

Indian J Radiol Imaging. 2013 Jul;23(3):243-6

Herlyn-Werner-Wunderlich syndrome presenting with infertility: Role of MRI in diagnosis.

Ahmad Z1Goyal A1Das CJ1Deka D2Sharma R1.

 

Abstract

Herlyn-Werner-Wunderlich syndrome (HWWS), characterized by uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis, is an uncommon combined Mullerian and mesonephric duct anomaly, and its presentation in adulthood is even rarer. We report here a 22-year-old female presenting with primary infertility where magnetic resonance imaging (MRI) suggested the diagnosis of HWWS with endometriosis. In a patient of infertility with endometriosis and unilateral renal agenesis, diagnosis of HWWS should be suspected and MRI is the investigation of choice for such anomalies.

 

 

Biomed Res Int. 2013;2013:436589.

The importance and perspective of magnetic resonance imaging in the evaluation of endometriosis.

Bianek-Bodzak A1Szurowska E2Sawicki S3Liro M3.

 

Abstract

MR imaging is becoming increasingly important in the assessment of patients with endometriosis. Its multiplanar capabilities and superior soft tissue contrast are particularly useful in the detection of deep infiltrating endometriotic implants. Endometriosis, defined as the presence of endometrial glands and stroma outside the endometrium, is among the most common gynaecological disorders affecting women in their reproductive age. The diagnosis and evaluation of the extension of endometriosis are difficult only with physical examination and laparoscopy. According to the authors’ personal experience, a special MRI technique and some imaging guidelines regarding different anatomical localizations of endometriosis are discussed. This review is a brief presentation of current evidence on the diagnostic accuracy of MRI in the evaluation of endometriosisconcerning other diagnostic methods, the limitations of MRI and its essential usefulness for preoperative diagnosis of deep pelvic endometriosis, and future perspectives in monitoring this disease.

 

 

Hum Reprod. 2014 Mar;29(3):462-72.

Occult microscopic endometriosis: undetectable by laparoscopy in normal peritoneum.

Khan KN1Fujishita AKitajima MHiraki KNakashima MMasuzaki H.

 

Abstract

STUDY QUESTION:

Is there any occurrence of hidden (occult) endometriotic lesions in normal peritoneum of women with and without visible endometriosis?

SUMMARY ANSWER:

We detected a slightly higher occurrence of occult microscopic endometriosis (OME) in normal peritoneum of women with visible endometriosis than in control women.

WHAT IS KNOWN ALREADY:

Based on a small number of cases, the concept of invisible microscopic endometriosis in visually normal peritoneum has been reported for more than a decade but there is controversy regarding their tissue activity and clinical significance.

STUDY DESIGN, SIZE, DURATION:

This case-controlled research study was conducted with prospectively collected normal peritoneal samples from 151 women with and 62 women without visible endometriosis.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Normal peritoneal biopsy specimens from different pelvic sites of were collected during laparoscopy. A histological search of all peritoneal biopsy specimens for the detection of invisible endometriosis was done by immunoreaction to Ber-EP4 (epithelial cell marker), CD10 (stromal cell marker) and Calretinin (mesothelial cell marker). Tissue expression of estrogen/progesterone receptors (ER/PR) and cell proliferation marker, Ki-67, was performed by immunohistochemistry to identify tissue activity.

MAIN RESULTS AND THE ROLE OF CHANCE:

Three different patterns of OME were detected based on (I) the presence of typical gland/stroma, (II) reactive hyperplastic change of endometrioid epithelial cells with surrounding stroma and (III) single-layered epithelium-lined cystic lesions with surrounding stroma. A higher tendency toward the occurrence of OME was found in women with visible endometriosis (15.2%, 23/151) compared with control women (6.4%, 4/62) (P = 0.06, χ(2) test). The epithelial cells and/or stromal cells of OME lesions were immunoreactive to Ber-EP4 and CD10 but not reactive to Calretinin. ER and PR expression was observed in all patterns of OME lesions. Ki-67 index was significantly higher in pattern I/II OME lesions than in pattern III OME lesions (P< 0.05 for each).

LIMITATIONS, REASONS FOR CAUTION:

Bias in the incidence rate of OME lesions in this study cannot be ignored, because we could not analyze biopsy specimens from the Pouch of Douglas of women with revised classification of the American Society of Reproductive Medicine Stage III-IV endometriosis due to the presence of adhesions in the pelvis.

WIDER IMPLICATIONS OF THE FINDINGS:

We re-confirmed a decade long old concept of invisible (occult) endometriosis in visually normal peritoneum of women with visible endometriosis. The existence of a variable amount of tissue activity in these occult lesions may contribute to the recurrence/occurrence of endometriosis or persistence/recurrence of pain manifestation in women even after successful ablation or excision of visible lesions by laparoscopy.

STUDY FUNDING/COMPETING INTEREST(S):

This work was supported in part by Grants-in-aid for Scientific Research from the Japan Society for the Promotion of Science. There is no conflict of interest related to this study.

 

 

Fertil Steril. 2014 Feb;101(2):442-6.

Bowel complications of deep endometriosis during pregnancy or in vitro fertilization.

Setúbal A1Sidiropoulou Z2Torgal M3Casal E3Lourenço C4Koninckx P5.

 

Abstract

OBJECTIVE:

To review bowel complications caused by deep endometriosis during pregnancy or in vitro fertilization (IVF).

DESIGN:

Three case reports and a systematic review.

SETTING:

A tertiary referral center for deep endometriosis surgery.

PATIENT(S):

Three case reports of bowel perforation or occlusion during pregnancy caused by deep endometriosis.

INTERVENTION(S):

A PubMed search was conducted to identify complications of deep endometriosis during pregnancy or IVF. The literature search identified 13 articles. According to these, 12 articles described 12 bowel complications caused by progression of deep endometriosis during pregnancy, and 1 article described six cases of bowel occlusion during IVF.

RESULT(S):

In 12 of 15 women, complications occurred during the third trimester of pregnancy, whereas 3 of 15 women presented with complications in the postpartum period. All complications during IVF occurred during stimulation. No specific factors that could predict these complications were identified, leading to the conclusion that endometriosis complications that occur in pregnancy or in IVF patients are probably underreported.

CONCLUSION(S):

Bowel complications during pregnancy or IVF stimulation may occur in women with deep endometriosis. This suggests that the endocrine environment of pregnancy does not prevent progression, at least in some women. These complications are rare, although probably underreported.

 

 

Abdom Imaging. 2014 Apr;39(2):398-410.

Imaging of complications associated with port access of abdominal laparoscopic surgery.

Han NY1Sung DJPark BJKim MJCho SBKim YH.

 

Abstract

Advanced techniques and equipment in laparoscopic surgery offer advantages over open surgery, expanding the application of this minimally invasive procedure to a wide range of abdominal operations that used to be performed as an open procedure. Laparoscopic surgery is performed in the closed abdominal cavity in which the space is limited. To create a working space in the abdominal cavity, an artificial pneumoperitoneum is established and multiple ports are placed for the introduction of various laparoscopic instruments. Unlike open surgery in which the incision is made just above the target organ, laparoscopic access is made away from the area of dissection, with the instruments triangulated around the target organ within the abdomen. This fundamental difference in approach between the open and laparoscopic procedures may lead to peculiar postoperative complications after laparoscopic surgery, which may be present away from the target organ or in the abdominal wall, and be easily missed on postoperative imaging studies. These complications include port-related direct organ injuries, such as abdominal organ or vascular injury; abdominal wall complications related to laparoscopic port insertion such as vascular injury, infection, and hernia; abdominal wall complications related to specimen removal, such as port site tumor seeding and endometriosis; and complications related to gas insufflation. The radiologist plays an important role in the diagnosis of complications after laparoscopic surgery, and therefore should be familiar with the features of such complications on imaging scans in the era of laparoscopic surgeries.

 

 

Ann Agric Environ Med. 2013;20(4):854-8.

Do inflammatory factors play a significant role in etiopathogenesis of endometrial cysts? Part 1.

Chmaj-Wierzchowska K1Kampioni M2Wilczak M3Opala T1.

 

Abstract

Endometriosis is an estrogen-related chronic condition which consists in the implantation and growth of endometrial cells outside the uterine cavity. It has an immune and inflammatory background, and to-date the precise etiopathogenesis of endometrial cysts has not been unequivocally defined. The objective of the study was evaluation of the indicators of the inflammatory state, including RANTES and the levels of C-reactive protein, leukocytes, fibrinogen and iron in the blood serum of patients with endometrial cysts (n=48) and benign ovarian tumours of mature teratoma type (n=38). Statistical analysis was performed using the Mann-Whitney Rank Sum Test. The p values p<0.05 were considered statistically significant.

RESULTS:

While comparing the results, respectively in groups, the mean levels in blood serum were as follows: RANTES 31,429.79 pg/ml (from 26,576.6-99,605.00) vs. 26,988.72 pg/ml (from 26,013.58-113,435.00) for p=0.428; CRP and WBC 2.13 vs. 1.54 mg/l; p=0.076 and 5.35 vs. 6.7; p=0.029; fibrinogen 3.12 vs. 2.57 mg%; p<0.001); iron level 87.20 vs. 78.01 ug/dl for p=0.430, and CA-125 36.50 vs. 15.08 U/ml; p<0.001).

CONCLUSIONS:

Statistically significant differences were observed in the levels of WBC, fibrynogen and CA-125 in blood serum. Therefore, the role of the inflammatory factor in the etiopathogenesis of endometrial cysts still remains unexplained, and the presented study may emerge as pioneer investigations in the area of etiology of endometriosis.

 

 

Reprod Biomed Online. 2014 Feb;28(2):232-8.

Pathophysiology proposed as the basis for modern management of the ovarian endometrioma.

Brosens I1Gordts S2Puttemans P2Benagiano G3.

 

Abstract

Present management of the ovarian endometrioma focuses on the size of the cyst and dictates that surgery should not be performed unless this exceeds 3 cm, which neglects the complex pathology of this condition. Studies of ovaries with the endometrioma in situ show progressive smooth muscle cell metaplasia and fibrosis of the cortical layer as the main ovarian lesion. There is no correlation between the size of the endometrial cyst and the degree of ovarian pathology: it is the mere presence of an ovarian endometrioma that has a detrimental impact on the cortical layer’s follicle reserve. Cystectomy in young patients with an endometrioma may be particularly detrimental to follicle reserve, with the ovarian parenchyma loss at the time of surgery being related to the cyst’s diameter. An underutilized diagnostic procedure, transvaginal hydrolaparoscopy with in-situ inspection of the cyst wall by ovarioscopy, allows careful diagnosis of ovarian pathology and selection of appropriate surgery with minimal invasiveness. Thus, available evidence shows that expectant management may not be the best choice when an endometrioma is suspected. On the contrary, early diagnosis through a minimally invasive technique, followed by early ablative surgery whenever indicated, represents the management of choice to preserve normal ovarian function. Present management of ovarian endometriomata is based on the size of the cyst and dictates that surgery should not be performed unless this exceeds 3cm. We argue that this approach neglects the true pathology of the ovary, since pioneers have studied ovaries with the endometrioma in situ and demonstrated that progressive smooth muscle cell metaplasia and fibrosis in the cortical layer constitute the main features of an endometrioma. There is no correlation between the size of the endometrial cyst and the degree of ovarian pathology: it is in the first place the mere presence of an ovarian endometrioma that has a detrimental impact on follicle reserve. It has been shown that cyst ablation in young patients with an endometrioma may be particularly detrimental to follicle reserve. An underutilized diagnostic procedure, transvaginal needle endoscopy with in-situ inspection after injection of saline suspension into the peritoneal cavity (hydrolaparoscopy) allows careful diagnosis of ovarian cortical pathology by colour changes from pearl-white to dark fibrotic. Thus, available evidence shows that expectant management may not be the best choice when an endometrioma is suspected: the delay in diagnosis causes delay in treatment and progression of the process leading to loss of follicles. On the contrary, early diagnosis through a minimally invasive technique, followed by early ablative surgery whenever indicated, represents the management of choice to preserve normal ovarian function.

 

 

Nat Rev Endocrinol. 2014 May;10(5):261-75.

Endometriosis: pathogenesis and treatment.

Vercellini P1Viganò P2Somigliana E1Fedele L1.

 

Abstract

Endometriosis is defined as the presence of endometrial-type mucosa outside the uterine cavity. Of the proposed pathogenic theories (retrograde menstruation, coelomic metaplasia and Müllerian remnants), none explain all the different types of endometriosis. According to the most convincing model, the retrograde menstruation hypothesis, endometrial fragments reaching the pelvis via transtubal retrograde flow, implant onto the peritoneum and abdominal organs, proliferate and cause chronic inflammation with formation of adhesions. The number and amount of menstrual flows together with genetic and environmental factors determines the degree of phenotypic expression of the disease. Endometriosis is estrogen-dependent, manifests during reproductive years and is associated with pain and infertility. Dysmenorrhoea, deep dyspareunia, dyschezia and dysuria are the most frequently reported symptoms. Standard diagnosis is carried out by direct visualization and histologic examination of lesions. Pain can be treated by excising peritoneal implants, deep nodules and ovarian cysts, or inducing lesion suppression by abolishing ovulation and menstruation through hormonal manipulation with progestins, oral contraceptives and gonadotropin-releasing hormone agonists. Medical therapy is symptomatic, not cytoreductive; surgery is associated with high recurrence rates. Although lesion eradication is considered a fertility-enhancing procedure, the benefit on reproductive performance is moderate. Assisted reproductive technologies constitute a valid alternative. Endometriosis is associated with a 50% increase in the risk of epithelial ovarian cancer, but preventive interventions are feasible.

 

 

Am J Physiol Endocrinol Metab. 2014 Mar 1;306(5):E483-93.

Porcine sst1 can physically interact with other somatostatin receptors, and its expression is regulated by metabolic/inflammatory sensors.

Gahete MD1Durán-Prado MDelgado-Niebla EGarrido JJRhodes SJGarcía-Navarro SGracia-Navarro FMalagón MMLuque RMCastaño JP.

 

Abstract

The majority of the biological actions attributed to somatostatin (SST) are thought to be mediated by SST receptor 2 (sst2), the most ubiquitous sst, and, to a lesser extent, by sst5. However, a growing body of evidence suggests a relevant role of sst1 in mediating SST actions in (patho)physiological situations (i.e., endometriosis, type 2 diabetes). Moreover, sst1 together with sst2 and sst5 is involved in the well-known actions of SST on pituitary somatotropes in pig and primates. Here, we cloned the porcine sst1 (psst1) and performed a structural and functional characterization using both primary and heterologous models. The psst1 sequence presents the majority of signature motifs shared among G protein-coupled receptors and, specifically, among ssts and exhibits a high homology with other mammalian sst1, with only minor differences in the amino-terminal domain, reinforcing the idea of an early evolutive divergence between mammalian and nonmammalian sst1s. psst1 is functional in terms of decreasing cAMP levels in response to SST when transfected in heterologous models. The psst1 receptor is expressed in several tissues, and analyses of gene cis elements predict regulation by multiple transcription factors and metabolic stimuli. Finally, psst1 is coexpressed with other sst subtypes in various tissues, and in vitro data demonstrate that psst1 can interact with itself forming homodimers and with other ssts forming heterodimers. These data highlight the functional importance of sst1 on the SST-mediated effects and its functional interaction with different ssts, which point out the necessity of exploring the consequences of such interactions.

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