Mol Med Rep. 2018 Mar 29. doi: 10.3892/mmr.2018.8823. [Epub ahead of print] Zearalenone regulates endometrial stromal…
Minerva Ginecol. 2015 Jun;67(3):257-72.
Robotic management of endometriosis: where do we stand?
The progressive and chronic nature of this disease can have a substantial impact on both quality of life and functioning of women who suffer from the disease. While medical treatment can be sufficient therapy for many women with endometriosis, medical therapies are often inadequate for the severest cases. The anatomic changes of adhesions/fibrosis and smooth muscle metaplasia that are associated with endometriosis, however, can be substantial and surgery for this disease can be technically challenging. Historically, the severest cases of endometriosis were managed using a laparotomy approach. Traditional laparoscopy has gained popularity for the management of this disease but has limitations in the surgical treatment of the most difficult cases of endometriosis. With the introduction of the robotic surgical platform, experience has gradually accumulated regarding its application for surgical management of deeply infiltrating endometriosis (DIE). It has been suggested that the robotic platform enables more complex dissections and may be the ideal modality for the surgical management of endometriosis. As both experience and technology expand, the robotic platform is being utilized by an increasing number of surgeons and for increasingly complex minimally invasive pelvic surgery. The literature analyzing its actual performance in the management of DIE, however, is only just manifesting. This review focus on the surgical management of endometriosis by robotic laparoscopy. Specifically we describe the unique surgical challenges of this disease. We also highlight the current state of the literature that analyzes the application of robotic laparoscopy to the various anatomic and clinical manifestations of endometriosis and critique outcomes as they apply to the safety, efficacy and cost of this modality for the management of endometriosis.
Arch Gynecol Obstet. 2015 Sep;292(3):619-28
Phytochemical analyses and effects of Alchemilla mollis (Buser) Rothm. and Alchemilla persica Rothm. in rat endometriosis model.
Küpeli Akkol E1, Demirel MA, Bahadır Acıkara O, Süntar I, Ergene B, Ilhan M, Ozbilgin S, Saltan G, Keleş H, Tekin M.
The aim of the present study is to evaluate the treatment potential of Alchemilla mollis (Buser) Rothm. and Alchemilla persica Rothm. in the experimentally induced endometriosis model in rats.
Endometriosis was surgically induced in rats by autotransplanting endometrial tissue to abdominal wall. Thirty-six rats were randomly divided into six groups. The groups were orally treated with the methanol:water (80:20) extracts of aerial parts and roots of A. mollis and A. persica. Buserelin acetate (20 mg) was used as the reference drug. The phytochemical contents of the most active extracts were determined by high performance liquid chromatography.
The cystic formation was determined to be significantly decreased with the aerial part extract of A. mollis. A reduction in the endometrioma was also determined for the aerial part extract of A. persica group. However, significant reduction on the levels of cytokine were recorded for the A. mollis aerial part extract group. Therefore, the phytochemical contents of the aerial part extracts of A. mollis. and A. persica were analyzed.
The results of the present study revealed that the aerial part extracts of A. mollis and A. persica could be beneficial in the treatment of endometriosis.
Neuroscience. 2015 Apr 16;291:272-8.
Activation of p38 MAPK in the rostral ventromedial medulla by visceral noxious inputs transmitted via the dorsal columns may contribute to pelvic organ cross-sensitization in rats with endometriosis.
Chen Z1, Xie F2, Bao M2, Li X2, Chao Y2, Lin C3, Guo R2, Zhang C2, Wu A2, Yue Y2, Guan Y4, Wang Y5.
Whether visceral organ cross-sensitization is involved in endometriosis-associated pain remains elusive. Previous studies have shown that visceral noxious stimuli may trigger a cascade of signal transductions in the rostral ventromedial medulla (RVM) via the spinal dorsal column (DC) pathway and the RVM plays a critical role in the descending control of visceral nociception. In the current study, we hypothesized that the p38 mitogen-activated protein kinase (MAPK) activation in the RVM by noxious visceral inputs from ectopic growths via the DC was involved in the development of pelvic organ cross-sensitization in established endometriosis. A rat model of experimental endometriosis was established. To examine ectopic growths-to-colon cross-sensitization, graded colorectal distention (CRD) was performed and abdominal withdrawal reflex (AWR) scores were recorded in female rats at 8weeks after the uterine or fat (control) auto-transplantation. Western blot study was carried out to examine the phosphorylated form and the total level of p38 MAPK protein in the RVM. Our results showed that lesions of bilateral DCs immediately following uterine or fat auto-transplantation in female rats significantly attenuated the later development of ectopic growths-to-colon cross-sensitization and the increased p38 MAPK activation in the RVM, as compared to sham DC lesions. Furthermore, intra-RVM microinjection of a p38 MAPK inhibitor (SB 203580), but not vehicle, in female rats with established endometriosis significantly attenuated ectopic growths-to-colon cross-sensitization and the increased activation of p38 MAPK in the RVM. These findings suggest that the noxious inputs from ectopic growths may activate p38 MAPK in the RVM via the DC, which may contribute to the development of ectopic growths-to-colon cross-sensitization in established endometriosis.
Reprod Sci. 2015 Sep;22(9):1107-14
Evidence for a Hypercoagulable State in Women With Ovarian Endometriomas.
Wu Q1, Ding D1, Liu X2, Guo SW3.
Endometriosis is a hormonal disease and also an inflammatory condition. Converging evidence indicates that inflammation and coagulation are 2 major host-defense systems that interact with each other. This study was undertaken to test the hypothesis that women with ovarian endometriomas are in a hypercoagulable state as manifested by the altered procoagulant factors and higher percentage of activated platelets in their peripheral blood. Two sets of participants were recruited. The first set consisted of 50 premenopausal women with endometriosis and 50 age-matched healthy women, and the second set consisted of 21 women with endometriosis and 17 age-comparable women without endometriosis. For the first set, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen, and other coagulation factors, along with their demographic, clinical, and anthropometric data, were measured/retrieved. For the second set, only the percentage of activated platelets in peripheral blood was evaluated. We found that women with endometriosishad a significantly shortened APTT and TT and elevated fibrinogen levels as compared with controls. They also had significantly higher percentage of circulating degranuated platelets, and the percentage was significantly reduced 1 month after surgical removal of endometriotic lesions. These findings provide evidence of a hypercoagulable state in women with endometriosis, reflecting the intimate relationship between coagulation and inflammation. They also suggest that these coagulation parameters such as APTT and fibrinogen and others could potentially be used for diagnostic or prognostic purposes. It also underpins the possibility for the use of antithrombotic therapy in the treatment of endometriosis.
J Reprod Immunol. 2015 Jun;109:66-73.
Addition of MCP-1 and MIP-3β to the IL-8 appraisal in peritoneal fluid enhances the probability of identifying women with endometriosis.
Borrelli GM1, Kaufmann AM2, Abrão MS3, Mechsner S4.
Chemokines have been associated with endometriosis. Our study was aimed at evaluating the levels of six chemokines–CXCL8 (IL-8), CXCL12 (SDF-1), CCL2 (MCP-1), CCL5 (RANTES), CCL19 (MIP-3β), and CCL21 (6-Ckine)–in the peritoneal fluid (PF) of patients with and controls without endometriosis by multiplexed cytokine assay. In this retrospective case-control study conducted at the Charité University Hospital, patients (n = 36) and controls (n = 27) were enrolled. The patients were separated into groups according to stage of the disease: I-II (n = 21), III-IV (n = 1 5), and according to clinical findings: peritoneal endometriosis (PE; n = 7), deep-infiltrating endometriosis (DIE) affecting the retrocervical area (n = 13) or the bowel/rectovaginal site (n = 14). The subjects were also separated according to the cycle phase: follicular (n = 14) or luteal (n = 8) and the previous use (n = 25) or not (n = 38) of hormones. PF was collected from all subjects (n = 63) consecutively during laparoscopy. The concentration of chemokines in the PF was assessed using Luminex(®) x-MAP(®) technology. Sensitivity and specificity were calculated. A model of multiple logistic regressions estimated the odds of endometriosis for each combination of the chemokines detected. We observed significantly higher concentrations of IL-8 (p < 0.001), MCP-1 (p = 0.014), and MIP-3β (p = 0.022) in the PF of women with endometriosis than in the controls. A joint evaluation revealed that elevated levels of the three chemokines had a positive endometriosis prediction value of 89.1%. The combined assessment of MCP-1, MIP-3β, and IL-8 concentration in PF improved the likelihood of identifying patients with endometriosis. Future studies should investigate this panel in peripheral blood samples.
Ultrasound Q. 2015 Mar;31(1):5-18.
The role of multimodality imaging after cesarean delivery.
Rezvani M1, Shaaban AM, Kennedy AM.
There has been a global increase in the rate of cesarean delivery during the last 30 years. As a result, many women of reproductive age now have uterine scars. Well-recognized obstetric and gynecologic consequences include cesarean scar pregnancy, scar dehiscence or rupture, and scar endometriosis. More recently, abnormal menstrual bleeding, pelvic pain, and secondary infertility have been reported as a consequence of cesarean delivery. This article reviews the range of normal imaging findings after cesarean delivery, as well as the imaging manifestations of complications, both acute and chronic.
Ultrasound Q. 2015 Mar;31(1):37-44.
ACR appropriateness Criteria® infertility.
Wall DJ1, Javitt MC, Glanc P, Bhosale PR, Harisinghani MG, Harris RD, Khati NJ, Mitchell DG, Nyberg DA, Pandharipande PV, Pannu HK, Shipp TD, Siegel CL, Simpson L, Wong-You-Cheong JJ, Zelop CM.
Appropriate imaging for women undergoing infertility workup depends upon the clinician’s suspicion for potential causes of infertility. Transvaginal US is the preferred modality to assess the ovaries for features of polycystic ovary syndrome (PCOS), the leading cause of anovulatory infertility. For women who have a history or clinical suspicion of endometriosis, which affects at least one third of women with infertility, both MRI and pelvic US can provide valuable information. If tubal occlusion is suspected, whether due to endometriosis, previous pelvic inflammatory disease, or other cause, hysterosalpingogram (HSG) is the preferred method of evaluation. To assess for anatomic causes of recurrent pregnancy loss (RPL) such as Müllerian anomalies, synechiae, and leiomyomas, saline infusion sonohysterography, MRI and 3-D US are most appropriate. Up to 10% of women suffering recurrent pregnancy loss have a congenital Müllerian anomaly. When assessment of the pituitary gland is indicated, MRI is the imaging exam of choice.The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
Biofizika. 2014 Jul-Aug;59(4):766-75.
Physico-chemistry of dinitrosyl iron complexes with thiol-containing ligands underlying their beneficial treatment of endometriosis.
Vanin AF, Adamian LV, Burgova EN, Tkachev NA.
Exogenous dinitrosyl iron complexes (DNIC) with thiol-containing ligands as NO and NO+ donors are capable of exerting both regulatory and cytotoxic effects on diverse biological processes similarly to those characteristic of endogenous nitric oxide. Regulatory activity of DNIC (vasodilation, hypotension, trombosis suppression, red blood cell elasticity increasing, skin wound healing acceleration, penile erection inducing, etc) is determined by their capacity of NO and NO+ transfer to biological targets of the latter (hemo- and thiol-containing proteins, respectively) due to higher affinity of the proteins for NO and NO+ than that of DNIC. Cytotoxic activity of DNIC is endowed with rapid DNIC decomposition under action of iron-chelating compounds resulting in appearance of NO and NO+ in cells and tissues in high amount. The latter mechanism is suggested to cause the blocking effect of DNIC as cytotoxic effectors on the development of benign endometrial tumors in rats with experimental endometriosis. It is also proposed that. a similar mechanism can operate causing at least a delay of malignant tumor proliferation under action of DNIC.
Ann Ital Chir. 2014 Dec 29;85(ePub)
Vulvar endometriosis and Nuck canal.
Mazzeo C, Gammeri E, Foti A, Rossitto M, Cucinotta E.
Endometriosis is not a well-known disease and sometimes its rare onset is a pathogenetic, diagnostic and therapeutic problem. The Canal of Nuck is an embryonal rest of the parietal peritoneum that accompanies the round ligament through the inguinal canal. The perviousness of the canal of Nuck could explain the pathogenesis of vulvar endometriosis.
MATERIAL OF STUDY:
We reported a case of vulvar endometriosis localization, which is rather uncommon, in a patient previously operated on with cyst of Nuck.
One of the most helpful instrumental exams in defining the nature of vulvar swallows is magnetic resonance, but it remains difficult to diagnose vulvar endometriosis in spite of the instrumental exam in our possession. The hypothesis of retrograde menstruation is supported by the fact that ovarian localization is the most common in this disease. Extra-pelvic localization as well as vulvar one are less common. The Canal of Nuck is an embryonal rest of the parietal peritoneum that accompanies the round ligament through the inguinal canal.
Endometriosis could be taken into consideration in differential diagnosis of vulvar swellings, and for this reason it is necessary to carry out a histological exam in every operated vulvar neoformation. We suggest vaginalis-peritonei duct contamination as a possible pathogenesis mechanism of this disease.
Int J Womens Health. 2015 Feb 9;7:205-11.
CYFRA 21-1 in urine: a diagnostic marker for endometriosis?
Diagnostic workup of endometriosis usually involves laparoscopic inspection and histological examination of biopsies. Unequivocal laboratory parameters for this ailment have not been available in routine diagnostic evaluations thus far. In this study, we examined urine concentrations of cytokeratin 19 (CYFRA 21-1), a structural protein specific for epithelia. We performed immunoassays for CYFRA 21-1 in urine samples from women afflicted with endometriosis throughout their menstrual cycle. We observed a significant increase in CYFRA 21-1 concentrations, corrected by creatinine levels, in the late follicular phase as compared with the level in healthy controls. We conclude that cyclically increased CYFRA 21-1 concentrations in urine could serve as a valuable noninvasive diagnostic parameter in the workup of clinically manifesting endometriosis.
Iran J Reprod Med. 2014 Nov;12(11):755-64.
High ω-3:ω-6 fatty acids ratio increases fatty acid binding protein 4 and extracellular secretory phospholipase A2IIa in human ectopic endometrial cells.
Khanaki K1, Sadeghi MR2, Akhondi MM3, Darabi M4, Mehdizadeh A4, Shabani M5, Rahimipour A6, Nouri M7.
Endometriosis, a common chronic inflammatory disorder, is defined by the atypical growth of endometrium- like tissue outside of the uterus. Secretory phospholipase A2 group IIa (sPLA2-IIa) and fatty acid binding protein4 (FABP4) play several important roles in the inflammatory diseases.
Due to reported potential anti-inflammatory effects of ω-3 and ω-6 fatty acids, the purpose of the present study was to investigate the effects of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) on fatty acid binding protein 4 and extracellular secretory phospholipase A2IIa in cultured endometrial cells.
MATERIALS AND METHODS:
Ectopic and eutopic endometrial tissues obtained from 15 women were snap frozen. After thawing and tissue digestion, primary mixed stromal and endometrial epithelial cell culture was performed for 8 days in culture mediums supplemented with normal and high ratios of ω-3 and ω-6 PUFA. sPLA2-IIa in the culture medium and FABP4 level was determined using enzyme immuno assay (EIA) technique.
Within ectopic endometrial cells group, the level of cellular FABP4 and extracellular sPLA2-IIa were remarkably increased under high ω-3 PUFA exposure compared with control condition (p=0.014 and p=0.04 respectively).
ω-3 PUFAs may increase the level of cellular FABP4 and extracellular sPLA2-IIa in ectopic endometrial cells, since sPLAIIa and FABP4 may affect endometriosis via several mechanisms, more relevant studies are encouraged to know the potential effect of increased cellular FABP4 and extracellular sPLA2-IIa on endometriosis.
J Res Med Sci. 2014 Dec;19(12):1145-9.
The diagnostic role of cervico-vaginal fluid interleukins-1α in endometriosis: A case-control study.
Mardanian F1, Sheikh-Soleimani Z1.
Endometriosis is a chronic and progressive gynecological disorder and is manifest by dysmenorrhea and a major cause of infertility and chronic pelvic pain. The study was designed to compare the value of cervico-vaginal fluid of interleukin-1α (IL-1α) in patients with and without endometriosis.
MATERIALS AND METHODS:
Fifty women were assessed in this case control study. The case group included 25 patients with endometriosis. The control group included 25 women without any evidence of endometriosis or any other genital disease. Endometriosis was confirmed by laparoscopy and histopathological examination. Cervico-vaginal fluid samples were obtained from patients during the follicular phase and preup surgery to assess the levels of IL-1α in cervico-vaginal fluid. The level of IL-1α was assessed using commercially available Avi Bionhuman Enzyme-Linked Immunosorbent Assay kits (FIN-01720, Vantaa, Finland) for IL-1α. Receiver-operator curve analysis was used to estimate the power of IL-1α to distinguish subjects with endometriosis from controls.
The cervico-vaginal fluid level of IL-1α in cases was 210.44 ± 40.11 pg/mL and in controls was 54.28 ± 25.73 pg/mL, the differences between two groups was statistically significant (P < 0.0001). The cut-off point for cervico-vaginal fluid IL-1 for endometriosis was 105 pg/mL, with a sensitivity of 100% (95% confidence interval [CI]: 86.2-100), and specificity of 100% (95% CI: 86.2-100).
Results show a significant increase in the cervico-vaginal fluid levels of IL-1α, in women with endometriosis, that it can be a useful marker in the diagnosis of endometriosis.
J Obstet Gynaecol. 2015;35(8):832-4.
Efficacy of transabdominal sonoelastography in the diagnosis of caesarean section scar endometrioma: A pilot study.
Transabdominal sonoelastography (TASE) is a new imaging technique that maps the elastic properties of soft tissue. We evaluated 34, consecutive women with suspected scar endometrioma using standard B-mode ultrasound and elastography. Twenty-three women (23/34) underwent surgical excision and had the diagnosis confirmed by histopathology. All endometriomas (23 patients) in B-mode imaging appeared as hypoechoic masses along the line of a previous caesarean section incision and the outer borders were difficult to define precisely. By TASE, the endometrioma presented a typical blue-green-red appearance and the outer borders were clearly defined. (red and green area corresponds with the central hypoechoic soft areas). Strain ratios varied from 0.02 to 0.75. Real-time TASE is a simple, useful technique in confirming a clinical diagnosis of endometrioma in a caesarean section scar. Compared with B-mode ultrasound, it provides additional, preoperative information about the extent of the lesion that may be helpful to the surgeon.
Genetika. 2014 Feb;50(2):230-5.
Association of matrix metalloproteinases’ polymorphisms of MMP3 and MMP9 with development of genital endometriosis.
Iarmolinskaia MI, Molotkov AS, Bezhenar’ VF, Shved NIu, Ivashchenko TE, Baranov VS.
We present a comparative analysis of the allelic polymorphism of the matrix metalloproteinase (MMP) gene family, including MMP3 (rs3025058), MMP7 (rs11568818), MMP9 (rs17576, rs2250889), MMP12 (rs2276109), and MMP13 (rs2252070), in patients with external genital endometriosis (EGE) and in a control group of healthy women proven to be free of disease by laparoscopic inspection. We found significant differences in the incidence of particular MMP3 and MMP9 alleles, which substantiate the role of matrix metalloproteinases in EGE pathogenesis. We used the Multifactor Dimensionality Reduction (MDR) analysis to show that 14 allelic combinations of the MMP containing MMP3 (rs3025058) x MMP7 (rs11568818) x MMP9 (rs17576) alleles showed a statistically significant association with an increased risk of EGE, while 10 other combinations correlated with a reduced risk of the disease. MDR analysis produced two statistically significant models for MMP allelic combinations involved in EGE progression, both with 100% penetrance and 83% and 78% accuracy.
Arch Gynecol Obstet. 2015 Sep;292(3):641-5.
Soluble CD44 concentration in the serum and peritoneal fluid samples of patients with different stages of endometriosis.
Mashayekhi F1, Aryaee H, Mirzajani E, Yasin AA, Fathi A.
Endometriosis is a gynecological disease defined by the histological presence of endometrial glands and stroma outside the uterine cavity, most commonly implanted over visceral and peritoneal surface within the female pelvis. CD44 is a membrane protein expressed by human endometrial cells, and it has been shown to promote the adhesion of endometrial cells. The aim of this study was to determine the levels of soluble CD44 (sCD44) in the serum and peritoneal fluid (PF) samples of patients with different stages of endometriosis.
39 PF and serum samples from normal healthy and 130 samples from different stages of patients with endometriosis (33 cases of stage I, 38 stage II, 30 stage III and 29 stage IV) were included in this study. Total protein concentration (TPC) and the level of s-cMet in the serum were determined by Bio-Rad protein assay based on the Bradford dye procedure and enzyme-linked immunosorbent assay, respectively.
No significant change in the TPC was seen in the serum of patients with endometriosis when compared to normal controls. Results obtained demonstrated that all serum and peritoneal fluid samples, presented sCD44 expression, whereas, starting from stages I to IV endometriosis, a significant increase of sCD44 expression was observed as compared to control group.
The results of this study show that a high expression of sCD44 is correlated with advanced stages of endometriosis. It is also concluded that the detection of serum and/or peritoneal fluid sCD44 may be useful in classifying endometriosis.
Acta Obstet Gynecol Scand. 2015 May;94(5):489-93.
Hysterectomy types in Estonia are still different from the Nordic countries.
Veerus P1, Lang K, Toompere K, Kirss F.
To describe hysterectomy rates in different age groups, indications and proportion of surgery types over time.
Nationwide register-based study.
Women who had hysterectomies for benign indications from 2004 to 2011.
For each case, diagnosis according to ICD-10, type of surgery according to Nordic Medico-Statistical Committee, age, and time of operation were retrieved from the Estonian Health Insurance Fund database. Mid-year female population statistics were obtained from Statistics Estonia.
MAIN OUTCOME MEASURES:
Rate of hysterectomies per 100 000 women, proportions of different operation types, and main indications for hysterectomies.
The total number of hysterectomies was 12 336, with a yearly mean of 1542. The rate of hysterectomies per 100 000 women/year decreased between 2004 and 2011 from 239.1 to 204.9. The proportion of abdominal hysterectomies decreased from 86.0 to 56.1% and the proportion of laparoscopic hysterectomies increased from 6.3 to 34.7%, while the proportion of vaginal hysterectomies remained more or less stable (7.8-9.1%). Most hysterectomies (74.4%) occurred in the age group 35-54 years. The main indications for hysterectomies were leiomyoma (61.5%), female genital prolapse (9.0%) and endometriosis (8.8%).
Population rates and indications for hysterectomies in Estonia were similar to those in most Nordic countries, but the proportion of abdominal hysterectomies was higher and that of vaginal hysterectomy lower. The rates of laparoscopic and vaginal hysterectomies should be increased.
Braz J Med Biol Res. 2015 Apr;48(4):363-9.
Reduction of blood nitric oxide levels is associated with clinical improvement of the chronic pelvic pain related to endometriosis.
Rocha MG1, Gomes VA2, Tanus-Santos JE3, Rosa-e-Silva JC4, Candido-dos-Reis FJ4, Nogueira AA4, Poli-Neto OB4.
The objective of this prospective study was to determine the plasma levels of nitric oxide (NO) in women with chronic pelvic pain secondary to endometriosis (n=24) and abdominal myofascial pain syndrome (n=16). NO levels were measured in plasma collected before and 1 month after treatment. Pretreatment NO levels (μM) were lower in healthy volunteers (47.0±12.7) than in women with myofascial pain (64.2±5.0, P=0.01) or endometriosis(99.5±12.9, P<0.0001). After treatment, plasma NO levels were reduced only in the endometriosis group (99.5±12.9 vs 61.6±5.9, P=0.002). A correlation between reduction of pain intensity and reduction of NO level was observed in the endometriosis group [correlation = 0.67 (95%CI = 0.35 to 0.85), P<0.0001]. Reduction of NO levels was associated with an increase of pain threshold in this group [correlation = -0.53 (-0.78 to -0.14), P<0.0001]. NO levels appeared elevated in women with chronic pelvic pain diagnosed as secondary to endometriosis, and were directly associated with reduction in pain intensity and increase in pain threshold after treatment. Further studies are needed to investigate the role of NO in the pathophysiology of pain in women with endometriosis and its eventual association with central sensitization.
Int J Surg Pathol. 2015 May;23(3):211-6.
Primary peritoneal clear cell carcinoma versus ovarian carcinoma versus malignant transformation of endometriosis: a vexing issue.
Insabato L1, Natella V2, Somma A2, Persico M2, Camera L2, Losito NS3, Masone S2.
Peritoneum is a site for both primary and secondary tumors. Primary peritoneal tumors are fairly rare. The most common primary tumors of the peritoneum are malignant mesothelioma and serous papillary adenocarcinoma. Clear cell carcinoma of the peritoneum is extremely rare and often misdiagnosed as mesothelioma, serous carcinoma, or metastatic adenocarcinoma, so it represents a diagnostic challenge for both clinicians and pathologists. Up to date, to the best of our knowledge, only 11 cases of primary peritoneal clear cell carcinoma have been reported in the English literature. Distinguishing this tumor of the peritoneum versus ovarian carcinoma can be problematic. Herein, we report a rare case of primary peritoneal clear cell carcinoma occurring in a 49-year-old woman, along with a review of the literature.
J Ultrasound Med. 2015 Mar;34(3):537-42
Deep infiltrating endometriosis of the bowel wall: the comet sign.
Benacerraf BR1, Groszmann Y2, Hornstein MD2, Bromley B2.
The purpose of this study was to evaluate the appearance of deep infiltrating endometriosis of the bowel wall in the cul-de-sac and determine the characteristic appearance of these lesions. We searched our database between January 1, 2011, and December 31, 2013, for all patients who had sonographic findings of suspected deep infiltrating endometriosis of the bowel with obliteration of the cul-de-sac. The medical record of each patient was examined retrospectively for evidence of surgical confirmation of disease. The sonographic appearance, shape, and size of the bowel wall lesions were evaluated to develop criteria for deep infiltrating endometriosis of the rectosigmoid and cul-de-sac. The search of our database revealed 35 patients with sonographic findings of pelvic bowel wall endometriosis associated with obliteration of the cul-de-sac. Ten of these patients had surgical confirmation of bowel wall endometriosis after the scan, and another 4 patients had surgical evidence of endometriosis from prior surgery. All of the patients who underwent surgery subsequent to sonography had confirmation of their bowel wall infiltrative endometriosis. Sonographically, the bowel lesions were solid, focal, and tubular with slightly irregular margins and in most cases a thinner section or a “tail” at one end, resembling a comet. This study confirms that bowel wall implants have a very characteristic appearance, and extending the transvaginal examination to include an evaluation of the rectosigmoid seeking these bowel lesions is valuable, especially in any patient presenting with a history of pelvic pain.
Cancer Res Treat. 2015 Oct;47(4):958-62
A Case of Metastatic Low-Grade Endometrial Stromal Sarcoma Treated with Letrozole after Ovarian Ablation by Radiotherapy.
Yang KH1, Shin JA1, Jung JH1, Jung HW1, Lee HR1, Chang S2, Park JY3, Yi SY1.
A 50-year-old woman was admitted to our hospital due to multiple lung nodules detected incidentally on a chest X-ray. A video-assisted thoracoscopic lung biopsy revealed low-grade endometrial stromal sarcoma (LG-ESS). She had undergone a simple hysterectomy 1 year earlier owing to a diagnosis of adenomyosis. A review of her previous hysterectomy specimen showed not endometriosis but LG-ESS. According to the patient’s levels of serum follicle stimulating hormone and estradiol, she was in the premenopausal state with retained and normally functioning ovaries. She then underwent ovarian ablation by radiotherapy, after which she was administered 2.5 mg of letrozole once per day. Three months later, the size of the metastatic nodules in both lungs had decreased. The patient was followed up for 24 months while continuing on letrozole, and maintained a partial remission. We report herein on a case of metastatic LG-ESS treated with letrozole after ovarian ablation by radiotherapy.
J Epidemiol. 2015;25(3):194-203.
Risk profiles for endometriosis in Japanese women: results from a repeated survey of self-reports.
Yasui T1, Hayashi K, Nagai K, Mizunuma H, Kubota T, Lee JS, Suzuki S.
The prevalence and risk factors for endometriosis may differ according to diagnosis methodologies, such as study populations and diagnostic accuracy. We examined risk profiles in imaging-diagnosed endometriosis with and without surgical confirmation in a large population of Japanese women, as well as the differences in risk profiles of endometriosis based on history of infertility.
Questionnaires that included items on sites of endometriosis determined by imaging techniques and surgical procedure were mailed to 1025 women who self-reported endometriosis in a baseline survey of the Japan Nurses’ Health Study (n = 15 019).
Two hundred and ten women had surgically confirmed endometriosis (Group A), 120 had imaging-diagnosed endometriosis without a surgical procedure (Group B), and 264 had adenomyosis (Group C). A short menstrual cycle at 18-22 years of age and cigarette smoking at 30 years of age were associated with significantly increased risk of endometriosis (Group A plus Group B), while older age was associated with risk of adenomyosis (Group C). In women with a history of infertility, a short menstrual cycle was associated with a significantly increased risk of endometriosis in both Group A and Group B, but risk profiles of endometriosis were different between Group A and Group B in women without a history of infertility.
Women with surgically confirmed endometriosis and those with imaging-diagnosed endometriosis without surgery have basically common risk profiles, but these risk profiles are different from those with adenomyosis. The presence of a history of infertility should be taken into consideration for evaluation of risk profiles.
Expert Rev Mol Diagn. 2015 Apr;15(4):557-80.
Diagnostic potential of peritoneal fluid biomarkers of endometriosis.
Endometriosis is defined as the presence of endometrial glands and stroma outside the uterus, in different parts of the peritoneal cavity. It affects up to 10% of reproductive-age women and up to 50% of women with infertility. Surgical diagnosis of endometriosis is still the gold standard, with no diagnostic biomarkers available. Medical therapies target the symptoms and not the disease itself, and surgical treatment cannot prevent recurrence. As peritoneal fluid reflects the altered peritoneal microenvironment of endometriosis patients, it can provide a wealth of information on pathophysiological processes and potential biomarkers. This report reviews the molecular biomarkers identified in peritoneal fluid over the last 5 years and discusses their potential applications for diagnosis, prognosis and drug therapy.
J Pediatr Endocrinol Metab. 2015 Jul;28(7-8):923-5.
A patient developing anaphylaxis and sensitivity to two different GnRH analogues and a review of literature.
Ökdemir D, Hatipoğlu N, Akar HH, Gül Ü, Akın L, Tahan F, Kurtoğlu S.
Gonadotropin-releasing hormone analogues are used in the treatment of prostate cancer, breast cancer, endometriosis, and uterine leiomyomas in adults and often in the treatment of precocious puberty in children. Many adverse effects have been reported for gonadotropin-releasing hormone analogues, but anaphylaxis is rarely reported as an adverse effect. Frequent cross-reactions, particularly during childhood, and diversity of the time of onset of anaphylactic manifestations complicate the diagnosis. A patient who exhibited anaphylactic allergic reactions to two different agents used in the treatment of central precocious puberty presented here because the case has an atypical course and is the first in the literature.
Gynecol Obstet Invest. 2015;79(3):195-200.
Expression of DJ-1 and mTOR in eutopic and ectopic endometria of patients with endometriosis and adenomyosis.
Guo J1, Gao J, Yu X, Luo H, Xiong X, Huang O.
Endometrial cells may aberrantly express molecules involved in invasion and migration, leading to endometriosis. The aim of this study was to investigate the expression of DJ-1 and phosphorylated mammalian target of rapamycin (p-mTOR) in ectopic and eutopic endometria of endometriosis and adenomyosis.
Endometrial specimens were obtained from healthy non-menopausal women (n = 17) or patients with ovarian endometriotic cysts (n = 48) or adenomyosis (n = 30) during January 2011 to June 2012. The expressions of DJ-1 and p-mTOR were evaluated by immunohistochemistry and western blotting methods.
The expressions of DJ-1 and p-mTOR were significantly higher in the ectopic endometria than those in the eutopic endometria of endometriosis and adenomyosis patients or normal endometria (FDR < 0.05). DJ-1 expression was positively correlated with the p-mTOR expression no matter at endometriosis (r = 0.736, FDR < 0.001) or adenomyosis (r = 0.809, FDR < 0.001).
DJ-1 protein may be involved in endometrial cells proliferation, migration and angiogenesis by modulating the PI3K/Akt/p-mTOR signaling pathway, which provides an underlying theoretical target for endometriosis and adenomyosis.
Reprod Sci. 2015 Sep;22(9):1122-8.
Deep Invasive Endometriosis Lesions of the Rectosigmoid May Be Related to Alterations in Cell Kinetics.
Bassi MA1, Arias V2, D’Amico Filho N3, Gueuvoghlanian-Silva BY4, Abrao MS1, Podgaec S5.
The aim of this study was to analyze cell kinetics through expression and apoptosis of topoisomerase 2-α (TOP2A), p53, and c-erb2 in rectosigmoid endometriotic lesions and in healthy endometrial tissue and to establish correlations between such findings and clinical data in patients with rectosigmoid endometriosis.
Sixty patients with rectosigmoid endometriosis and 20 control women without endometriosis were included. Immunohistochemical assays were used to measure expression of TOP2A, p53, and c-erB-2. Apoptosis was quantified by directly counting the apoptotic bodies.
The number of lesions was positively correlated with expression of TOP2A in the lesion. There was also significant correlation between the lesions’ size and number and cell turnover index. Apoptosis index (AI) was the same for endometriosis lesions and eutopic endometrium. Expression of TOP2A was significantly lower in the endometriosis group compared to the controls.
Changes in cell proliferation but not in the AI in rectosigmoid endometriosis are indicative of an imbalance in cell kinetics that may lead to the development of the disease.
Gynecol Obstet Invest. 2015;79(3):189-94.
Human chorionic gonadotropin improves endometriosis through downregulation of leptin expression in rats.
Wu LL1, Pang RP, Yin YZ, Shen KF, Zhang PZ.
To investigate whether and how human chorionic gonadotropin (HCG) treatment ameliorates endometriosis in an endometriotic rat model.
Twenty-four endometriosis rats were established and were randomly divided into four groups, and then the rats were treated with 19.4, 25.8, and 51.6 IU/100 g weight/day of HCG, respectively. The control group was treated with 0.9% NaCl. After 15 days (3 estrous cycles), the ectopic lesion volume and the expression of leptin protein in eutopic and ectopic endometrium were investigated.
After HCG treatment, the volumes of endometriotic lesions were significantly smaller than those before treatment. During endometriosis development, the expression of leptin protein in eutopic and ectopic endometrium was remarkably increased. HCG administration reversed leptin upregulation in endometriotic tissues.
HCG therapy appears to be an effective treatment for endometriosis in rats through down-regulation of leptin expression in eutopic and ectopic endometrium.
Biomed Res Int. 2015;2015:461024.
Identification of susceptibility genes for peritoneal, ovarian, and deep infiltrating endometriosis using a pooled sample-based genome-wide association study.
Borghese B1, Tost J2, de Surville M2, Busato F2, Letourneur F3, Mondon F3, Vaiman D3, Chapron C1.
Characterizing genetic contributions to endometriosis might help to shorten the time to diagnosis, especially in the most severe forms, but represents a challenge. Previous genome-wide association studies (GWAS) made no distinction between peritoneal endometriosis (SUP), endometrioma (OMA), and deep infiltrating endometriosis(DIE). We therefore conducted a pooled sample-based GWAS and distinguished histologically confirmed endometriosis subtypes. We performed an initial discovery step on 10-individual pools (two pools per condition). After quality control filtering, a Monte-Carlo simulation was used to rank the significant SNPs according to the ratio of allele frequencies and the coefficient of variation. Then, a replication step of individual genotyping was conducted in an independent cohort of 259 cases and 288 controls. Our approach was very stringent but probably missed a lot of information due to the Monte-Carlo simulation, which likely explained why we did not replicate results from “classic” GWAS. Four variants (rs227849, rs4703908, rs2479037, and rs966674) were significantly associated with an increased risk of OMA. Rs4703908, located close to ZNF366, provided a higher risk of OMA (OR = 2.22; 95% CI: 1.26-3.92) and DIE, especially with bowel involvement (OR = 2.09; 95% CI: 1.12-3.91). ZNF366, involved in estrogen metabolism and progression of breast cancer, is a new biologically plausible candidate for endometriosis.
Am J Surg Pathol. 2015 Jul;39(7):983-92.
Ovarian seromucinous carcinoma: report of a series of a newly categorized and uncommon neoplasm.
Seromucinous neoplasms are a new category of ovarian epithelial tumor in the revised World Health Organization Classification of Tumours of the Female Reproductive Organs. Borderline variants are well described, but there have been few reports of seromucinous carcinomas. We report the clinicopathologic features in 19 cases of ovarian seromucinous carcinoma in patients aged 16 to 79 years (mean 47). In 16 cases, the neoplasm was unilateral and in 3 cases bilateral. The tumors ranged in size from 1.8 to 18 cm (mean 10.5 cm). The tumors were stage I (n=15), stage II (n=1), and stage III (n=3). The histologic features were highly variable both within and between individual tumors. The majority of neoplasms (12 cases) exhibited a predominant papillary architecture with lesser components of glandular, microglandular, and solid growth. A predominant glandular architecture was present in 6 cases, whereas 1 had a predominantly solid growth. A characteristic feature was an admixture of cell types. Most of the tumors (15 cases) were mainly composed of endocervical-like mucinous cells, whereas in 4 cases there was predominant endometrioid differentiation. Other cell types, present in varying proportions, included hobnail cells, eosinophilic cells, squamous cells, clear cells, and signet-ring cells. An infiltrate of neutrophil polymorphs was a prominent feature in most cases. Most cases also exhibited areas of microglandular architecture with cytoplasmic clearing and intraluminal polymorphs, the features closely resembling cervical microglandular hyperplasia. Areas of stromal hyalinization, adenofibromatous growth, and psammoma bodies were present in a minority of cases. Endometriosis was identified in the same ovary in 10 cases, and in 10 there was a component of seromucinous borderline tumor. Thirteen, 5, and 1 tumor were of grades 1, 2, and 3, respectively (using the FIGO grading system for endometrioid adenocarcinomas of the uterine corpus). A synchronous uterine endometrioid adenocarcinoma was present in 1 case. Immunohistochemically, there was positive staining with CK7 (17/17 cases), estrogen receptor (16/16 cases), progesterone receptor (6/7 cases), CA125 (15/15 cases), PAX8 (8/8 cases), CEA (8/13 cases), CA19.9 (8/9 cases), and WT1 (2/13 cases). CK20 and CDX2 were negative in all cases tested (16 and 14, respectively). p53 showed “wild-type” staining in 4/4 cases, and p16 was focally positive in 5/5 cases. Follow-up information was available in 8 patients. Seven were alive with no evidence of disease (follow-up 3 to 74 mo), whereas 1 patient who initially presented with a stage IIB tumor died of disease at 192 months. Given the characteristic admixture of cell types and the overlapping morphologic features with low-grade serous, mucinous, and endometrioid neoplasms, the most appropriate categorization of seromucinous carcinomas is uncertain, but we believe they are best regarded as a distinct type of ovarian epithelial malignancy and are most similar to endometrioid adenocarcinomas. We recommend grading them in an analogous manner to ovarian endometrioid adenocarcinomas.
Zentralbl Chir. 2016 Dec;141(6):630-638
Interdisciplinary Diagnosis and Treatment of Deep Infiltrating Endometriosis.
Alkatout I1, Egberts JH2, Mettler L1, Doniec M3, Wedel T4, Jünemann KP5, Becker T2, Jonat W1, Schollmeyer T1.
Endometriosis is the second most common benign female genital disease after uterine myoma. This review discusses the interdisciplinary approach to the treatment of deep infiltrating endometriosis. Endometriosis has been defined as the presence of endometrial glands and stroma outside the internal epithelial lining of the cavum uteri. As a consequence, endometriosis can cause a wide range of symptoms such as chronic pelvic pain, subfertility, dysmenorrhea, deep dyspareunia, cyclical bowel or bladder symptoms (e.g., dyschezia, bloating, constipation, rectal bleeding, diarrhoea and hematuria), abnormal menstrual bleeding, chronic fatigue or low back pain. Approx. 50 % of teenagers and up to 32 % of women of reproductive age, operated for chronic pelvic pain or dysmenorrhoea, suffer from endometriosis. The time interval between the first unspecific symptoms and the medical diagnosis of endometriosis is about 7 years. This is caused not only by the non-specific nature of the symptoms but also by the frequent lack of awareness on the part of the cooperating disciplines with which the patients have first contact. As the pathogenesis of endometriosis is not clearly understood, a causal treatment is still impossible. Treatment options include expectant management, analgesia, hormonal medical therapy, surgical intervention and the combination of medical treatment before and/or after surgery. The correct treatment for each patient should take into account the severity of the disease and whether the patient desires to have children. The treatment should be as radical as necessary and as minimal as possible. The recurrence rate among treated patients lies between 5 and > 60 % and is very much dependent on the integrated management and surgical skills of the respective hospital. Consequently, to optimise the individual patient’s treatment, a high degree of interdisciplinary cooperation in diagnosis and treatment is crucial and should, especially in the case of deep infiltrating endometriosis, be undertaken in appropriate centres.
Immunogenetics. 2015 Apr;67(4):203-9
KIR2DS5 in the presence of HLA-C C2 protects against endometriosis.
Nowak I1, Płoski R, Barcz E, Dziunycz P, Kamiński P, Kostrzewa G, Milewski Ł, Roszkowski PI, Senitzer D, Malejczyk J, Kuśnierczyk P.
Endometriosis is defined as the presence of functional endometrial tissue outside the uterine cavity. Several hypotheses have attempted to explain the etiology and pathogenesis of endometriosis. Recently, it has been suggested that a defect of the natural killer (NK) activity in the recognition and lysis of endometrial cells is one of the crucial points in the development of this disease. Natural killer cells can express killer immunoglobulin-like receptors (KIR), which recognize class I human leukocyte antigens on target cells. We asked whether polymorphisms in KIR, HLA-C, and HLA-B genes are risk factors for endometriosis. We tested 153 women with endometriosis diagnosed on the basis of laparoscopic and histological examination, and 213 control healthy women, who gave birth to at least one child. The frequency of KIR genes in patients was similar to that in controls except for KIR2DS5, which exerted a protective effect only in HLA-C C2-positive individuals. Moreover, KIR2DS5-positive women with endometriosis had 13 times lower chance that the disease would occupy the peritoneum than KIR2DS5- and KIR2DS4del-negative ones (OR = 0.077, P = 0.0061). Similarly, KIR2DS4del-positive endometriotic persons had 11 times lower chance for peritoneal disease (OR = 0.094, P < 0.001). Negative linkage disequilibrium between KIR2DS5 and KIR2DS4del indicates that these genes are mutually exclusive. Our data suggest that KIR2DS5 may be associated with protection from endometriosis, whereas KIR2DS4del seems to be associated with higher disease stages, possibly by exclusion of protective KIR2DS5.
Fertil Steril. 2015 May;103(5):1228-35.
G protein-coupled estrogen receptor 1 agonist G-1 induces cell cycle arrest in the mitotic phase, leading to apoptosis in endometriosis.
Mori T1, Ito F2, Matsushima H2, Takaoka O2, Tanaka Y2, Koshiba A2, Kusuki I2, Kitawaki J2.
To demonstrate the effects of the selective G protein-coupled estrogen receptor 1 (GPER) agonist G-1 in human ovarian endometriotic stromal cells (ESCs).
Experimental in vitro study.
A total of 33 patients with ovarian endometrioma.
Endometriotic stromal cells from ovarian chocolate cysts were treated with the GPER agonist G-1.
MAIN OUTCOME MEASURE(S):
The primary outcomes were cell proliferation, measured using the WST-8 assay; cell cycle, as analyzed using flow cytometry, fluorescent immunocytochemistry, and cytotoxicity; caspase activity, as measured by fluorescent and luminescent enzyme assays; and protein expression levels, as determined by Western blot analysis.
G-1 suppressed ESC proliferation in a concentration-dependent manner. The inhibitory effect was not blocked when GPER signaling pathways, including the GPER itself, were inhibited. G-1 induced cell cycle arrest and accumulation in the sub-G1 phase in ESCs. Immunofluorescence analysis demonstrated that G-1 interrupted microtubule assembly at the mitotic phase. G-1 also induced caspase-3-dependent apoptosis without significant cytotoxicity.
G-1 suppressed proliferation and induced apoptosis in ESCs, suggesting the potential use of this compound as a therapeutic drug for the treatment of endometriosis.
Gastroenterol Rep (Oxf). 2016 Aug;4(3):257-9.
Endometriosis mimicking colonic stromal tumor.
Wadhwa V1, Slattery E2, Garud S2, Sethi S2, Wang H3, Poylin VY4, Berzin TM5.
Endometriosis is defined as the presence of endometrial glands and stroma at extra-uterine sites; it is a common disease affecting women of reproductive age. Endometrial tissue can implant itself to various organs, including the gastrointestinal tract, and can cause significant gastrointestinal symptoms. These ectopic endometrial tissue implants are usually located in the pelvis but can be present almost anywhere in the body. Endometriosis seems to be the most frequent cause of chronic pelvic pain in women of reproductive age and may cause prolonged suffering and disability that negatively affect health-related quality of life. We report a case in a generally healthy young female patient who presented for evaluation of diarrhea.
Mymensingh Med J. 2015 Jan;24(1):70-3.
Quality and quantity of infertility care in Bangladesh.
Fatima P1, Ishrat S, Rahman D, Banu J, Deeba F, Begum N, Anwary SA, Hossain HB.
Infertility is an important health issue which has been neglected in the developing countries. First test-tube babies (triplet) in Bangladesh were born on 30th May, 2001. Although there is no tertiary level infertility center in the public sector, several private centers have come up with the facilities. The objective of the study was to find i) the quality and quantity of infertility care in Bangladesh and ii) the cause of infertility in the attending patients iii) the treatment seeking behaviors iv) and the reasons for not taking treatment among the attending patients. There are now 10 tertiary level Infertility centers in Bangladesh. The information was collected in a preformed datasheet about the facilities and the profile of the patients and the treatment seeking behavior of the attending patients. Out of the ten centers two centers refused to respond and did not disclose their data. Around 16700 new patients are enrolled in a year in the responsive clinics. Five percent (5%) of the patients underwent ART, 7% of the patients gave only one visit, 84% of the patients completed their evaluation, 76% of the patients took treatment. Causes of infertility in the patients taking treatment were male factor in 36.4%, bilateral tubal block in 20.2%, PCOS and anovulation in 31.7%, endometriosis in 19.6%, unexplained in 10.95, combined in 3.5%, ovarian failure in 1.4%, testicular failure in 0.33%, congenital anomaly in 0.3%. The main reason for not taking treatment was financial constrainment. The quality and quantity of infertility care is dependent on the available resources and on the use of the resources by the patients. In developing countries the resources are merging and confined to specified areas which cannot meet the demand of their population. The study gives us the idea of the need and the demand of the services in the country.
Ultrasound Obstet Gynecol. 2015 Dec;46(6):730-6.
Transvaginal sonographic features of diffuse adenomyosis in 18-30-year-old nulligravid women without endometriosis: association with symptoms.
Pinzauti S1, Lazzeri L1, Tosti C1, Centini G1, Orlandini C1, Luisi S1, Zupi E1, Exacoustos C2, Petraglia F1.
To investigate whether there are sonographic features of diffuse adenomyosis in 18-30-year-old nulligravid women without endometriosis and to examine their association with symptoms of dysmenorrhea and abnormal uterine bleeding.
This was a prospective observational study including women referred from a gynecology outpatient center to our university hospital for ultrasound examination. Inclusion criteria were age between 18 and 30 years, regular menstrual cycle and nulligravid status. Exclusion criteria were a past or current history of endometriosis, fibroids, ovarian cysts or lesions, endometrial pathology, current use of hormonal treatments or medications that would affect the menstrual cycle, previous uterine surgery and history of infertility. Women underwent a detailed clinical assessment and a two- (2D) and three-dimensional (3D) transvaginal ultrasound (TVS) examination. 2D-TVS features associated with diffuse adenomyosis were predefined as: (1) heterogeneous myometrium; (2) hypoechoic striation in the myometrium; (3) myometrial anechoic lacunae or cysts; (4) asymmetrical myometrial thickening of the uterine walls with the presence of straight vessels, extending into the hypertrophic myometrium, on power Doppler examination. On 3D-TVS, endomyometrial junctional zone (JZ) was measured as the distance from the basal endometrium to the internal layer of the outer myometrium on coronal section at any level of the uterus, and the smallest (JZmin) and largest (JZmax) JZ thicknesses and their difference (JZdiff) were recorded. 3D-TVS evaluation was considered suggestive for adenomyosis when JZmax ≥ 8 mm and/or JZdiff ≥ 4 mm. The presence of associated symptomatology represented our main outcome: the amount of menstrual loss was assessed by a pictorial blood loss analysis chart (PBAC) and painful symptoms were evaluated using a visual analog scale (VAS).
During the observation period, 205 women (median age, 24 (interquartile range, 23-27) years) were enrolled into the study and 156 met the inclusion criteria. According to the 2D-TVS criteria, diffuse adenomyosis was found in 53 (34.0%) women and asymmetrical myometrial thickening of the uterine walls was the most common sonographic feature observed. ANOVA showed a significant relationship between the number of 2D-TVS features of diffuse adenomyosis and VAS score for dysmenorrhea (P = 0.005) as well as PBAC score for menstrual loss (P = 0.03). 3D-TVS showed that women with 2D-TVS features of diffuse adenomyosis had a significantly higher value of JZmax (6.38 ± 2.30 mm, P < 0.001), JZmin (2.07 ± 0.43 mm, P = 0.002) and JZdiff (4.33 ± 1.99 mm, P < 0.001) than did women without these features. Women with sonographic features of diffuse adenomyosis were symptomatic in 83% of cases, reported dysmenorrhea in 79.2% and showed a higher incidence of heavy bleeding than did those without these features (18.9% vs 2.9%; P = 0.001).
Sonographic features suggestive of diffuse adenomyosis may develop earlier in reproductive life than previously thought, and may occur in association with dysmenorrhea and abnormal uterine bleeding in nulligravid women. Their observation in these women should therefore warrant further gynecological investigation.
J Minim Invasive Gynecol. 2015 May-Jun;22(4):691-3
A very rare case of endometriosis presenting with massive hemoperitoneum.
Togami S1, Kobayashi H2, Haruyama M2, Orita Y2, Kamio M2, Douchi T2.
Endometriosis is a cause of acute abdomen because of the leakage or rupture of endometriotic cyst and tubo-ovarian abscess. However, massive hemoperitoneum as a cause of acute abdomen with endometriosis is very rare. We herein present a case of a 48-year-old woman who was urgently referred to our clinic with colic, abdominal distension, and hypovolemic shock during menstruation. Ultrasonography revealed massive hemorrhagic ascites. Exploratory laparoscopy was urgently performed to achieve hemostasis. The volume of hemoperitoneum evacuated from the pelvis was 1,890 mL. Although the uterus and bilateral ovaries were normal, fresh bleeding was observed from endometriosis on the left cul-de-sac peritoneum, and hemostasis was successfully performed. The potential occurrence of hemorrhagic shock associated with endometriosis, depending on the implantation site, needs to be recognized.
Phlebology. 2015 Mar;30(1 Suppl):73-80
Clinical outcome after treatment of pelvic congestion syndrome: sense and nonsense.
Meissner MH1, Gibson K2.
Chronic pelvic pain accounts for approximately 10% of outpatient gynecologic visits and among the varied causes, pelvic congestion syndrome is second only to endometriosis in frequency. Manifestations may include pelvic pain, dyspareunia, dysuria, and dysmenorrhea as well as external varices and a number of psychosocial symptoms. Although a variety of treatments have been proposed-including pharmacologic ovarian suppression, hysterectomy with or without oophorectomy, and ovarian vein resection-transcatheter embolization is the least invasive and most efficacious management option. Complete or partial symptom improvement has been reported in 68.2-100% of patients and there has been a consistent reduction in visual analog pain scores after treatment. Based upon these results, recommendation of either pharmacotherapy or other surgical procedures is difficult to justify. However, it is also clear that 6-31.8% of patients do not get substantial relief from pelvic venous embolization. Potential explanations for an inadequate response to treatment include patient variability, procedural variability, and inadequate outcome measures. The latter are particularly important and future investigation should focus on the development of disease-specific quality of life measures as well as identifying those aspects of the procedure, such as choice of embolic agents and extent of embolization, associated with the best clinical outcomes.
Obstet Gynecol. 2015 Mar;125(3):719-28.
Association of chronic pelvic pain and endometriosis with signs of sensitization and myofascial pain.
Stratton P1, Khachikyan I, Sinaii N, Ortiz R, Shah J.
To evaluate sensitization, myofascial trigger points, and quality of life in women with chronic pelvic pain with and without endometriosis.
A cross-sectional prospective study of women aged 18-50 years with pain suggestive of endometriosis and healthy, pain-free volunteers without a history of endometriosis. Patients underwent a physiatric neuromusculoskeletal assessment of clinical signs of sensitization and myofascial trigger points in the abdominopelvic region. Pain symptoms, psychosocial, and quality-of-life measures were also assessed. All participants with pain underwent laparoscopic excision of suspicious lesions to confirm endometriosis diagnosis by histologic evaluation.
Patients included 18 with current, biopsy-proven endometriosis, 11 with pain only, and 20 healthy volunteers. The prevalence of sensitization as measured by regional allodynia and hyperalgesia was similar in both pain groups (83 and 82%) but much lower among healthy volunteers (15%, P<.001). Nearly all women with pain had myofascial trigger points (94 and 91%). Adjusting for study group, those with high anxiety (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.004-1.099, P=.031) and depression (OR 1.06, 95% CI 1.005-1.113, P=.032) scores were more likely to have sensitization. Pain patients with any history of endometriosis had the highest proportion of sensitization compared with the others (87% compared with 67% compared with 15%; P<.001). Adjusting for any history of endometriosis, those with myofascial trigger points were most likely sensitized (OR 9.41, 95% CI 1.77-50.08, P=.009).
Sensitization and myofascial trigger points were common in women with pain regardless of whether they had endometriosis at surgery. Those with any history of endometriosis were most likely to have sensitization. Traditional methods of classifying endometriosis-associated pain based on disease, duration, and anatomy are inadequate and should be replaced by a mechanism-based evaluation, as our study illustrates.
Arch Gynecol Obstet. 2015 Sep;292(3):647-54.
Prognostic value of preoperative Ca125 and Tag72 serum levels and their correlation to disease relapse and survival in endometrial cancer.
Myriokefalitaki E1, Vorgias G, Vlahos G, Rodolakis A.
To evaluate preoperative serum levels of Ca125 and Tag72-4 tumour markers and investigate if abnormal levels correlate to mortality and disease-free survival.
Retrospective observational study of a cohort of 282 women (mean age 62.3, SD 10.5 years) with primary endometrial cancer included all consecutive cases treated in a tertiary Gynaecological oncology Center. Excluded cases with other cancer or previous cancer treatment, major abdominal pathology or inflammation, endometriosis. Preoperative serum Tag72 and Ca125 levels were determined and evaluated in relation to disease-free survival (DFS) and disease-specific overall survival (DOS).
Raised Ca125 correlates to worse overall disease-specific survival (66.1 vs 87.8 months, p = 0.021) and Tag72 correlates to shorter disease-free survival (69.2 vs 67.3 months, p = 0.021) and higher recurrence rate (13.5 vs 6 %, p = 0.021). When both Ca125 and Tag72 are abnormal DFS and DOS are worse. 93.3 % (72.3 months) vs 82.4 %, (61.3 months) p = 0.018 and 96.3 % (74.8 months) vs 88.2 %, (65.9 months) p = 0.021, respectively.
This study enhances the value of preoperative tumour markers and their prognostic value. Ca125 and Tag72 appear to be good predictors of poor prognosis in patients with endometrial cancer.
Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):E1382-91
Activation of protein synthesis in mouse uterine epithelial cells by estradiol-17β is mediated by a PKC-ERK1/2-mTOR signaling pathway.
Wang Y1, Zhu L1, Kuokkanen S2, Pollard JW3.
The uterine epithelium of mice and humans undergoes cyclical waves of cell proliferation and differentiation under the regulation of estradiol-17β (E2) and progesterone (P4). These epithelial cells respond to E2 with increased protein and DNA synthesis, whereas P4 inhibits only the E2-induced DNA synthetic response. Here we show that E2 regulates protein synthesis in these epithelial cells through activating PKC that in turn stimulates ERK1/2 to phosphorylate and thereby activate the central regulator of protein synthesis mechanistic target of rapamycin (mTOR). This mTOR pathway is not inhibited by P4. Inhibitor studies with an estrogen receptor (ESR1) antagonist showed the dependence of this mTOR pathway on ESR1 but that once activated, a phosphorylation cascade independent of ESR1 propagates the pathway. E2 also stimulates an IGF1 receptor (IGF1R) to PI3 kinase to AKT to GSK-3β pathway required for activation of the canonical cell cycle machinery that is inhibited by P4. PKC activation did not stimulate this pathway nor does inhibition of PKC or ERK1/2 affect it. These studies therefore indicate a mechanism whereby DNA and protein synthesis are regulated by two ESR1-activated pathways that run in parallel with only the one responsible for the initiation of DNA synthesis blocked by P4. Inhibition of mTOR by rapamycin in vivo resulted in inhibition of E2-induced protein and DNA synthesis. Proliferative diseases of the endometrium such as endometriosis and cancer are common and E2 dependent. Thus, defining this mTOR pathway suggests that local (intrauterine or peritoneal) rapamycin administration might be a therapeutic option for these diseases.
Semin Reprod Med. 2015 Mar;33(2):65-76
Prognostic factors for IVF success: diagnostic testing and evidence-based interventions.
Papathanasiou A1, Bhattacharya S2.
Numerous tests and interventions have been proposed for optimizing performance in preparation for in vitro fertilization (IVF) treatment. We critically appraised the available evidence underpinning some of the popular investigations and treatments, including the role of hysteroscopy, laparoscopy, ovarian reserve tests, sperm function tests, as well as the role of lifestyle modifications or surgery for endometriosis, fibroids, and endometrial polyps. We also reviewed the evidence behind novel techniques, such as the use of endometrial injury before IVF. Only a few of the aforementioned modalities are justified based on the available research evidence. Other factors may affect the uptake of a test or intervention before IVF, namely the complexity of the proposed modality, its potential for harm, and its cost-effectiveness.
Ultraschall Med. 2015 Dec;36(6):623-9.
Elastography Improves the Accuracy of Ultrasound in the Preoperative Assessment of abdominal wall endometriosis.
Wozniak S, Czuczwar P, Szkodziak P, Wozniakowska E, Milart P, Paszkowski M, Paszkowski T.
To assess the role of elastography in preoperative ultrasound assessment of abdominal wall endometriosis (AWE) location.
MATERIALS AND METHODS:
33 patients qualified for surgical excision of AWE were included in the study. Preoperative assessment of AWE was performed transabdominally on a Samsung Medison V20 Prestige with a transvaginal probe and Elastoscan® option. The following B-mode settings were used: focus set to the lower end of the lesion, gain adjusted to obtain best image quality, tissue harmonic imaging activated. For elastographic examinations the color map from red (soft) to purple (hard) and the alpha blend option (a blend of B-mode and elastographic image) were used. AWE location was first assessed by B-mode ultrasound as: superficial (located in SCT only; SCT visible between the fascia and the lesion; intact fascia), intermediate (located in SCT or in RAM; no subcutaneous or muscle tissue between the lesion and the fascia; fascia infiltrated); or deep (located in RAM; muscle tissue visible between the lesion and the fascia; fascia intact). Then the AWE location was assessed by alphablend elastography as: superficial (hard lesion in soft SCT; soft SCT between the fascia and the lesion; no hard areas on the fascia); intermediate (hard lesion in soft SCT or soft RAM; no soft subcutaneous or muscle tissue between the lesion and the fascia; hard areas on the fascia); or deep (hard lesion located in RAM; soft muscle tissue between the fascia and the lesion; no hard areas on the fascia). These findings were verified during surgery. The surgeons were blinded to the results of elastography. The influence of obesity on the accuracy of ultrasound and elastography in assessing the location of AWE was evaluated.
During surgery superficial AWE was found in 6, intermediate in 19 and deep in 8 patients. Preoperative ultrasound assessment was correct in 33.3 % of cases, while adding the elastography option improved the accuracy of AWE location assessment to 87.9 % (p < 0.05). The diagnostic accuracy of ultrasound alone, but not with the elastography option, was significantly decreased in the preoperative assessment of AWE location in overweight and obese patients. 4 patients required implantation of a mesh. In all cases the pathological examination confirmed the diagnosis of AWE.
Elastography significantly improved the accuracy of ultrasound in evaluating the depth of infiltration of AWE, is not affected by increased BMI, and should be considered in patients qualified for surgical treatment of AWE.
Nan Fang Yi Ke Da Xue Xue Bao. 2015 Feb;35(2):281-3.
Lentiviral vector-mediated short hairpin RNA targeting survivin inhibits abdominal growth of human endometrium xenograft in nude mice.
To investigate the inhibitory effect of lentiviral vector-mediated short hairpin RNA targeting survivin (LV-survivin shRNA) on the growth of human endometrium xenograft in the abdominal cavity of nude mice.
The endometrium xenografts from 8 women with endometriosis were injected into the peritoneal cavities of 45 nude mice. The mice were then randomly assigned to receive intraperitoneal injection of LV-survivin shRNA, pGCL-NC-GFP (negative control) or PBS (blank control). Two weeks later, the number and morphometry of endometriotic lesions were quantified and the expression of survivin protein were detected by immunohistochemistry.
The formation of endometriotic lesions was significantly suppressed in mice receiving LV-survivin shRNA injection as compared with those in the two control groups (P/0.001). The mice in LV-survivin-shRNA group showed significantly down-regulated expression levels of survivin protein compared with those in the negative and blank control groups, presenting also necrosis in the endometriosis-like lesions in microscopic observation.
Lentiviral vector-mediated shRNA can effectively inhibit the expression of survivin in human endometrium xengrafts and suppress the formation and growth of endometriotic lesions in the abdominal cavities of nude mice.
J Obstet Gynaecol India. 2015 Feb;65(1):11-6
Treatment of endometriosis in women desiring fertility.
Endometriosis is a common condition affecting a significant proportion of women in their reproductive age. Apart from the impact of endometriosis on the quality of life of these patients, it also can have an impact on the potential of these women to have a family. The options for treating women with endometriosis desiring a family include surgery or assisted reproduction techniques. The choice of treatment will depend on the stage of disease and the characteristics of the couple seeking help. We review here the latest evidence on the management of endometriosis in women desiring fertility and describe our current practice.
J Obstet Gynaecol India. 2015 Feb;65(1):39-44.
Deciding the route for hysterectomy: Indian triage system.
To review the limitations, major complications, and conversion rates associated with non-descent vaginal hysterectomy (NDVH); and develop a scoring system to predict the possibility of successful NDVH.
The risk analysis of conversion rates from vaginal to abdominal route while attempting NDVH was applied to formulate a scoring system for the assessment of successful NDVH. Parameters were selected based on Kovacs guidelines to determine the route of hysterectomy.
From April 2005 to December 2008, NDVH was attempted in 364/1,378 women undergoing hysterectomy for benign conditions (Gp-I). Eight out of 364 cases (2.1 %) either had to be converted to the abdominal route or had major complication. Endometriosis and repeated sections had the highest risk. Scoring system was developed based on the risk analysis. Validity of this scoring system was tested in 1,177 women from January 2009 to September 2012 (Gp-II). 460 women with a score of 16 or less underwent NDVH successfully with a conversion rate of 0.2 %.
Careful assessment by a simple scoring system can help in deciding the feasibility of performing NDVH.
Eur J Obstet Gynecol Reprod Biol. 2015 Apr;187:25-9.
Ethanol sclerotherapy of ovarian endometrioma: a safe and effective minimal invasive procedure. Preliminary results.
García-Tejedor A1, Castellarnau M2, Ponce J3, Fernández ME3, Burdio F4.
To study if ultrasound-guided aspiration with ethanol sclerosis is a safe and effective treatment for endometriomas.
We conducted a prospective study of 25 women with 27 endometriomas (two bilateral) measuring 4-10cm in diameter with no suspected malignancy, who underwent ultrasound-guided aspiration and ethanol sclerosis between August 2010 and July 2014. Patients were followed up by ultrasound at 6, 12, 24, and 36 months to identify rates of complication and recurrence. Clinical characteristics of the patients (age, history of infertility, previous surgery, and abdominal pain), the cysts (location, diameter, and volume) and the procedure (duration and complications) were recorded. Kaplan-Meier survival curves were used to analyze the recurrence rates by SPSS statistical software.
The recurrence rate after sclerosis was 12%. The mean length of follow-up was 17 (SD 9.9) months. Although no major procedure-related complications were recorded, minor complications included three cases of low abdominal pain during the procedure (10.7%) and two cases of abdominal ethanol extravasation (7.1%).
Ultrasound-guided aspiration and ethanol sclerotherapy are a safe and effective treatment for endometriomas measuring 4-10cm in diameter with no evidence of malignancy. This conservative treatment could possibly achieve a symptomatic cure while preserving healthy ovarian tissue, thereby improving fertility outcomes and avoiding early menopause.
Eur J Obstet Gynecol Reprod Biol. 2015 Apr;187:35-40.
Correlation between three-dimensional rectosonography and magnetic resonance imaging in the diagnosis of rectosigmoid endometriosis: a preliminary study on the first fifty cases.
Philip CA1, Bisch C2, Coulon A3, de Saint-Hilaire P2, Rudigoz RC2, Dubernard G4.
Deep infiltrating endometriosis (DIE) raises a number of diagnostic and therapeutic problems. Magnetic resonance imaging (MRI), the reference technique in endometriosis, is questioned for posterior pelvic lesions, especially in rectosigmoid locations. In this study, we describe a new technique called three-dimensional rectosonography (3D-RSG), which combines standard transvaginal ultrasonography (TVUS), 3-dimensional (3D) ultrasonography and the use of water for rectal contrast. We also assess the correlation between 3D-RSG and MRI in the diagnosis of rectosigmoid endometriosis.
This study included 50 consecutive women with symptoms suggestive of DIE. After colorectal enema, they underwent a gynecological examination and a 3D TVUS during which 120ml of water was injected in the rectosigmoid to improve the performance of the examination. All patients also underwent an MRI and surgery was offered to the patient if there was discordance between the two procedures.
Fifty women underwent 3D-RSG between May and November 2012. All procedures were well tolerated by patients. Two examinations (4%) were stopped for technical reasons. Nineteen rectosigmoid nodules were diagnosed in 18 women (36%). Eighteen of these nodules were also identified on MRI, and one (2%) nodule seen on MRI was not diagnosed by 3D-RSG. In 31 examinations (62%), neither technique identified an intestinal lesion. There was a concordance rate of 96% between the two techniques. Using MRI as the reference technique, 3D-RSG had a sensitivity of 0.95, a specificity of 0.97, a positive predictive values of 0.95, and a negative predictive value of 0.97. There was a 30.3 positive likelihood ratio and a 0.05 negative likelihood ratio.
3D-RSG seems an interesting new method for diagnosis of rectosigmoid endometriosis and is both feasible and well tolerated. 3D-RSG is highly concordant with MRI in this indication, although further studies are needed to confirm these primary results.
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