Bull Exp Biol Med. 2017 Feb;162(4):539-544.

Characteristics of Multipotent Mesenchymal Stromal Cells Isolated from the Endometrium and Endometriosis Lesions of Women with Malformations of the Internal Reproductive Organs.

Savilova AM¹, Farkhat KN², Yushina MN², Rudimova YV², Makiyan ZN², Adamyan LV².

 

Abstract

We isolated and characterized cell cultures from eutopic endometrium and endometriotic lesions of women with malformations of the internal reproductive organs. The cells had fibroblast-like shape and intensively expressed CD90, CD73, CD105, CD44, CD146, and CD117 and were capable of induced adipogenic and osteogenic differentiation in vitro. The obtained cultures exhibited properties of multipotent mesenchymal stromal cells; at the same time, they demonstrated in vitro immunophenotypic differences from cell cultures of eutopic and ectopic endometrium of women without developmental abnormalities, which suggests their functional difference. The cells from eutopic endometrium and from ectopic endometriotic lesions can be used as the model for studying of the etiology and pathogenesis of endometriosis and for testing new drugs for this specific group of patients. Markers CD90 and CD117 were identified as promising molecules for the development of minimally invasive diagnostics of endometriosis based on cell cultures from eutopic endometrium.

 

 

Asian Pac J Cancer Prev. 2017 Jan 1;18(1):11-16.

Endometriosis and Ovarian Cancer: an Integrative Review (Endometriosis and Ovarian Cancer)

Brilhante AV¹, Augusto KL, Portela MC, Sucupira LC, Oliveira LA, Pouchaim AJ, Nóbrega LR, Magalhães TF, Sobreira LR.

 

Abstract

Despite being initially considered a benign disease, it is widely thought nowadays that endometriosis and especially ovarian endometriomas are neoplastic conditions with the potential to become malignant. This review was conducted to summarize, in a concise and systematic manner, the available scientific data relating endometriosis to ovarian cancer, published in the past five years. After reading abstracts and applying our predefined inclusion and exclusion criteria, a final list of 11 scientific papers was obtained and subjected to review. Endometriosis is associated with an increased risk of developing epithelial ovarian cancer (EOC), mainly of endometrioid and clear cell subtypes. This might be by virtue of the high estrogen concentration with the disease, which leads to malignant proliferation of endometriotic cysts, or be due to mutations in the ARID1A gene and consequent loss of BAF250a expression. The iron produced in the fluid of endometriotic cysts promotes oxidative stress, which in turn may cause genetic mutations and malignant progression of ovarian cysts.

 

 

Am J Reprod Immunol. 2017 Aug;78(2)

The CCL17-CCR4 axis between endometrial stromal cells and macrophages contributes to the high levels of IL-6 in ectopic milieu.

Zhou WJ¹, Hou XX¹, Wang XQ¹, Li DJ¹.

 

Abstract

Endometriosis is a chronic inflammatory disease characterized by the elevation of proinflammatory cytokines, such as IL-6, in the peritoneal fluid. However, the precise mechanism of the highly elevated IL-6 levels in ectopic milieu remains unclear. The aim of this study was to investigate whether the cross talk between endometrial stromal cells (ESCs) and macrophages contributes to the elevated IL-6 production. Samples of endometrium and ectopic tissues were obtained from patients with or without endometriosis. The peripheral blood samples were collected from healthy volunteers. Enzyme-linked immunosorbent assay (ELISA) was for IL-6 levels in peritoneal fluid and cell culture supernatant. In-Cell Western assay was used for protein expression of CCL17 and phosphorylation levels of ERK, JNK, and P38. Immunohistochemistry was performed on normal, eutopic endometrium and ectopic tissues to analyze CCL17 expression. Flow cytometry was applied to detect the expression of CCR4, IL-6, and the phosphorylation levels of NF-κB. Patients with endometriosis have higher levels of IL-6 in peritoneal fluid compared to the control. The co-culture of ESCs and macrophages produce more IL-6 than cultured alone, respectively. The eutopic endometrium had significantly higher expression of CCL17 compared to normal endometrium, and the ectopic tissues had the highest expression. IL-6 induced CCL17 secretion in ESCs via activating JNK signaling pathway, CCL17 upregulated the expression of its receptor CCR4 on macrophages. Furthermore, CCL17-CCR4 axis subsequently led to excessive IL-6 production in macrophages by activating NF-κB. These findings suggest that the cross talk between ESCs and macrophages promotes the expression of CCL17 in ESCs and CCR4 on macrophages, which contributes to the high levels of IL-6 in ectopic milieu.

 

 

Minerva Ginecol. 2017 Oct;69(5):440-446.

Abdominal wall endometriosis following cesarean section: a study of the growth rate of parietal endometriosis implants.

Touleimat S¹, Darwish B¹, Vassilieff M¹, Stochino Loi E², Hennetier C¹, Roman H^3,4.

Abstract

BACKGROUND:

The study aimed to estimate the growth rate of abdominal wall endometriosis (AWE) following cesarean section (CS), in order to potentially identify a growth model of endometriosis in vivo.

METHODS:

This monocentric, retrospective study included 23 patients presenting 26 nodules of post-CS AWE treated by surgical excision. Nodule surface and volume, time-lapse between surgery and AWE as well as the contraception used were noted. A comparison between nodules’ features was performed depending on hormonal vs. non-hormonal contraception.

RESULTS:

The time-lapse between CS and AWE surgery had a mean value of 48 months. The mean surface of an AWE nodule was of 3.83 cm2, and the mean volume was of 5.32 cm3. Comparison between the main surface and volume in patients receiving hormonal vs. non-hormonal contraception was statistically non-significant. No statistically significant correlation between AWE dimension and time was revealed. In patients presenting more than one lesion, nodules appeared to grow following variable patterns.

CONCLUSIONS:

AWE natural history was characterized by inter- and intra-individual variability, independently of the method of contraception used.

 

 

Rev Bras Ginecol Obstet. 2017 Jan;39(1):31-34.

Tubocutaneous Fistula due to Endometriosis – A Differential Diagnosis in Cutaneous Fistulas with Cyclic Secretion.

Lopes EN¹, Damásio LC¹, Passos LS¹.

 

Abstract

The development of a tubocutaneous fistula due to endometriosis in a post-cesarean section surgical scar is a rare complication that generates significant morbidity in the affected women. Surgery is the treatment of choice in these cases. Hormonal therapies may lead to an improvement in symptoms, but do not eradicate such lesions. In this report, we present a 34-year-old patient with a cutaneous fistula in the left iliac fossa with cyclic secretion. Anamnesis, a physical examination, and supplementary tests led us to suggest endometriosis as the main diagnosis, which was confirmed after surgical intervention.

 

 

World J Gastroenterol. 2017 Feb 14;23(6):1113-1118.

Pancreatic endometrial cyst mimics mucinous cystic neoplasm of the pancreas.

Mederos MA¹, Villafañe N¹, Dhingra S¹, Farinas C¹, McElhany A¹, Fisher WE¹, Van Buren Ii G¹.

 

Abstract

Pancreatic cysts include a variety of benign, premalignant, and malignant lesions. Endometrial cysts in the pancreas are exceedingly rare lesions that are difficult to diagnose pre-operatively. This report describes the findings in a 43-year-old patient with a recent episode of acute pancreatitis who presented with a large cyst in the tail of the pancreas. Imaging demonstrated a loculated pancreatic cyst, and cyst fluid aspiration revealed an elevated amylase and carcinoembryonic antigen. The patient experienced an interval worsening of abdominal pain, fatigue, diarrhea, and a 15-pound weight loss 3 mo after the initial episode of pancreatitis. With concern for a possible pre-malignant lesion, the patient underwent a laparoscopic distal pancreatectomy with splenectomy, which revealed a 16 cm × 12 cm × 4 cm lesion. Final histopathology was consistent with an intra-pancreatic endometrial cyst. Here we discuss the overlapping imaging and laboratory features of pancreatic endometrial cysts and mucinous cystic neoplasms of the pancreas.

 

 

Aust N Z J Obstet Gynaecol. 2017 Feb;57(1):87-92.

Clinicians’ perceptions of women’s experiences of endometriosis and of psychosocial care for endometriosis.

Young K¹, Fisher J¹, Kirkman M¹.

Abstract

BACKGROUND:

Endometriosis is a complex, chronic condition with known psychological and social implications for women. Little is known about clinicians’ perceptions of the psychosocial aspects of endometriosis and associated care.

AIM:

To describe clinicians’ perceptions of women’s experiences of living with endometriosis and of the provision of psychosocial care for endometriosis.

MATERIALS AND METHODS:

A qualitative approach was taken using semi-structured interviews with eight gynaecologists and four general practitioners who provide care to women with endometriosis in Victoria, conducted by telephone and in person from June to December 2014.

RESULTS:

Clinicians’ perceptions of women’s experiences of endometriosis were consistent with those reported by women, particularly when discussing potential infertility. However, less comprehensive descriptions of the effects of endometriosis on women’s work and social life and intimate relationships were observed. Some clinicians asserted that endometriosis is caused by poor mental health. General practitioners positioned themselves as best placed to provide psychosocial care to women with endometriosis; gynaecologists suggested various potential providers but rarely themselves. Most clinicians assessed themselves as not being adequately trained to understand and provide care for the psychosocial aspects of endometriosis; half of the gynaecologists did not believe it was necessary for them to do so.

CONCLUSIONS:

The findings of this research demonstrate clinicians’ need for further support in the provision of psychosocial care for women with endometriosis, potentially through expanded clinical guidelines and professional development opportunities.

 

 

Taiwan J Obstet Gynecol. 2017 Feb;56(1):55-61.

Unexpected epithelial ovarian cancers arising from presumed endometrioma: A 10-year retrospective analysis.

Kuo HH¹, Huang CY¹, Ueng SH², Huang KG¹, Lee CL³, Yen CF⁴.

Abstract

OBJECTIVE:

To evaluate the incidence and prognosis of unexpected epithelial ovarian cancers (EOCs) occurring in presumed benign endometrioma.

MATERIALS AND METHODS:

Patients who underwent primary surgery at Chang Gung Memorial Hospital between November 2003 and October 2013 were searched with the Systematized Nomenclature of Medicine code followed by chart review.

RESULTS:

The incidence of unexpected EOCs in presumed ovarian endometrioma was 0.14%, as 11 patients were revealed after reviewing 497 patients of pathology-proven EOCs in the current series. All patients were aged ≥ 40 years; seven (63.6%) had inward mass within ovarian cyst in preoperative images, six had cancer antigen-125 (CA-125) > 200 U/mL, and two with CA-125 > 1500 U/mL. Ten patients underwent laparoscopy initially, including five with ovarian preservation at the beginning. Ten patients subsequently completed concurrent or secondary staging surgery, including four totally with laparoscopy. The histologic subtypes had clear-cell (8/11), endometrioid (1/11), mixed clear-cell and endometrioid (1/11), and low-grade serous adenocarcinoma (1/11). Seven patients had endometriosis-associated ovarian carcinoma (EAOC), while the other four were non-EAOC with no endometriosis component. The only mortality was a patient of non-EAOC in Stage IIIc, whereas the other 10 in Stage I were alive. The overall survival rate was 90.9% (10/11) with follow-up ranging from 23 months to 130 months.

CONCLUSION:

Unexpected EOCs occurring in presumed ovarian endometrioma was rare and, if present, the prognosis was good in Stage I disease with laparoscopic management. Combining parameters of patient’s age, CA-125 level, and inward solid mass at imaging could help to raise the precautions.

 

 

J Minim Invasive Gynecol. 2017 May – Jun;24(4):677-682.

Case Report: Laparoscopic Uterovaginal Anastomosis for Congenital Isolated Cervical Agenesis.

Scibilia G¹, Pecorino B², Pagano I¹, Scollo P¹.

 

Abstract

Management of cervical agenesis is a challenge owing to the complexity of the malformation and the difficulty in restoring and preserving fertility. We propose a minimally invasive fertility-sparing surgery for a 17-year-old woman with congenital cervical agenesis and a normal vagina and uterus confirmed by vaginoscopy. The patient was admitted for primary amenorrhea, hematometra, and cyclic pelvic pain. She had undergone previous laparoscopies for ovarian endometriosis. Our surgical approach involved the creation of an isthmus-vaginal anastomosis with a uterovaginal reconnection. After surgery, the patient experienced regular menstrual cycles without dysmenorrhea. At 12 months postsurgery, she continued to experience normal menstruation, and the uterovaginal connection had not stenosed. Management of congenital cervical agenesis requires accurate diagnosis that includes appropriate classification of the malformation (European Society of Human Reproduction and Embryology/European Society for Gynaecological Endoscopy classification). Surgical treatment is controversial and depends on the patient’s age and desire for resolution.

 

 

 

J Robot Surg. 2017 Mar 2.

Visualization of endometriosis: comparative study of 3-dimensional robotic and 2-dimensional laparoscopic endoscopes.

Mosbrucker C¹, Somani A², Dulemba J³.

 

Abstract

The main objective of this study was to compare results of using the robotic 3D/HD scope and the 2D/HD laparoscope for visual detection of histologically confirmed endometriosis. Three surgeons from different practices enrolled premenopausal women ≥18 years who had elected to undergo robotic-assisted endometriosisresection. Patients were randomized to receive 2D/HD laparoscopic visualization either before or after 3D/HD robotic visualization. Resections then proceeded robotically. The number of histologically confirmed lesions overall and by abdomino-pelvic location, appearance and size was compared by scope type used. During the study, 598 lesions were visualized in 98 patients. Average number of lesions per patient using either scope was 6.1. Mean age was 31 years and 77% were disease stage I/II. On histopathology, 58.4% of lesions resected were consistent with endometriosis. All (100%) of these lesions were detected using the robotic 3D/HD scope and 77.9% using the 2D/HD laparoscope (p < 0.001). Compared to laparoscopic, robotic visualization resulted in detection of more confirmed lesions in all anatomic locations and for most appearances, including the cul-de-sac (100 vs. 79%), atypical appearance (100 vs. 71.3%) and width <5 mm (100 vs. 62%), p’s < 0.001). Logistic regression indicated that use of the 3D/HD robotic scope was independently associated with 2.36 times the likelihood (95% CI 1.20, 4.66; p = 0.014) of detecting a confirmed lesion, compared to the 2D/HD laparoscope. Large-scale, long-term studies are needed to substantiate these findings in multiple practice settings and to determine whether 3D robotic versus 2D laparoscopic resection has a beneficial impact on symptomatology, recurrence and fertility outcomes.

 

 

Arch Gynecol Obstet. 2017 Apr;295(4):827-832.

Research development of a new GnRH antagonist (Elagolix) for the treatment of endometriosis: a review of the literature.

Alessandro P¹, Luigi N², Felice S², Maria PA³, Benedetto MG³, Stefano A³.

Abstract

PURPOSE:

Limitated studies have reported the efficacy of GnRH antagonist on endometriosis symptoms. The aim of our study was to review all available trials to investigate the medical treatment of endometriosis with only GnRH antagonists, with special attention to pharmacodynamic activity, safety, and efficacy.

METHODS:

Pub Med and Sciencedirect database were searched using terms of “endometriosis treatment”, “GnRH antagonist”, and “Elagolix”. The search was limited to clinical studies published in English. Title and abstract were screened to identify relevant articles.

RESULTS:

Five studies covering use of GnRH antagonist were found. A phase 1 study evaluated the safety, pharmacokinetics, and inhibitory effects on gonadotropins and estradiol of single dose and 7 day elagolix administration to healthy premenopausal women; two phase II studies evaluated efficacy in patient with endometriosis. Moreover, there are two Phase III clinical trials just completed.

CONCLUSION:

GnRH antagonists may have the advantage of oral administration and lower incidence of adverse events. Currently, only Phase II studies have been published demonstrating promising results in terms of efficacy, safety, and tolerability. From the results of the phase III studies, elagolix may become a valuable addition to the armamentarium of pharmacological agents to treat endometriosis-related pain.

 

 

Fertil Steril. 2017 Apr;107(4):1070-1077.

Mu opioid receptor in the human endometrium: dynamics of its expression and localization during the menstrual cycle.

Totorikaguena L¹, Olabarrieta E¹, Matorras R², Alonso E³, Agirregoitia E¹, Agirregoitia N⁴.

Abstract

OBJECTIVE:

To study the dynamics of the expression and localization of the mu opioid receptor (MOR) in human endometrium throughout the menstrual cycle.

DESIGN:

Analysis of human endometrial samples from different menstrual cycle phases (menstrual, early/midproliferative, late proliferative/early secretory, midsecretory, and late secretory) by reverse transcription-polymerase chain reaction, Western blot, and immunohistochemistry.

SETTING:

Academic research laboratory.

PATIENT(S):

Women from the Human Reproduction Unit of the Cruces University Hospital, fulfilling the following criteria: normal uterine vaginal ultrasound; absence of endometriosis, polycystic ovary syndrome, implantation failure, or recurrent miscarriage; and no history of opioid drug use.

INTERVENTION(S):

Endometrial samples of 86 women categorized into groups for the menstrual cycle phases: 12 menstrual, 21 early/midproliferative, 16 late proliferative/early secretory, 17 midsecretory, and 20 late secretory.

MAIN OUTCOME MEASURE(S):

MOR gene and protein expression and localization in the different compartments of the human endometrium at different stages of the menstrual cycle.

RESULT(S):

The expression of MOR mRNA and protein changed throughout the cycle in human endometrium. MOR expression increased during the proliferative phase and decreased during the secretory one. Lower values were found at menstruation, and maximum values around the time of ovulation. Small variations for each endometrial compartment were found.

CONCLUSION(S):

The presence of MOR in human endometrium and the dynamic changes during the menstrual cycle suggest a possible role for opioids in reproduction events related to the human endometrium or endometriosis.

 

 

Gynecol Obstet Fertil Senol. 2017 Mar;45(3):131-136.

Comparison of the accuracy of rectal endoscopic sonography and magnetic resonance imaging in the diagnosis of colorectal endometriosis.

Kanté F¹, Belghiti J², Roseau G³, Thomassin-Naggara I⁴, Bazot M⁵, Daraï E⁶, Ballester M⁷.

Abstract

OBJECTIVE:

To compare the accuracy of magnetic resonance imaging (MRI) and rectal endoscopic sonography (RES) for the diagnosis of colorectal endometriosis.

METHODS:

In retrospective study, 407 patients operated on service of gynecology of Tenon hospital for deep endometriosis with suspected colorectal involvement. All patients underwent MRI and then RES.

RESULTS:

In the study, 239 patients (59%) had colorectal endometriosis which were diagnosed with the histology. The sensitivity, specificity, positive and negative predictive value (PPV and NPV) of RES and MRI for the diagnosis of colorectal endometriosis were respectively 92%, 87%, 91%, 88% and 85%, 88%, 91%, 80%. The accuracy of RES was not significantly different than MRI (90% versus 86%, P=0.09).

CONCLUSION:

RES is a good exam to diagnose colorectal endometriosis. It is able to improve diagnosis performances.

 

 

Biol Psychiatry. 2017 Jan 16. pii: S0006-3223(17)30038-0.

Psychotherapy With Somatosensory Stimulation for Endometriosis-Associated Pain: The Role of the Anterior Hippocampus.

Beissner F¹, Preibisch C², Schweizer-Arau A³, Popovici RM⁴, Meissner K⁵.

Abstract

BACKGROUND:

Endometriosis is a gynecological disorder affecting 6%-10% of all women in their reproductive age. There is an emerging view in the literature that psychological trauma plays a central role in the pathogenesis of pelvic pain, one of the core symptoms of endometriosis. Here we report central nervous system mechanisms of a novel combination of psychotherapy and somatosensory stimulation that has recently shown remarkable effects in reducing pain, anxiety, and depressive symptoms in these patients.

METHODS:

We conducted a randomized controlled trial; 67 patients with severe endometriosis-associated pain (maximum pain: 7.6 ± 2.0, average pain: 4.5 ± 2.0 on a 10-point numeric rating scale) were included in the study and randomly allocated to intervention (35 patients) or waitlist control (32 patients) groups. Resting-state functional magnetic resonance imaging was used to assess brain connectivity of these patients at baseline, after 3 months of therapy, and after 6 months. The analysis focused on the hippocampus.

RESULTS:

We identified a cortical network comprising the right anterolateral hippocampus-a region modulating the hypothalamic-pituitary-adrenal axis-and somatosensory, viscerosensory, and interoceptive brain regions. Regression analysis showed that reduction in connectivity predicted therapy-induced improvement in patients׳ anxiety.

CONCLUSIONS:

We have identified a putative neurobiological mechanism underlying the potent combination of psychotherapy and somatic stimulation in treating symptoms of endometriosis.

 

 

Fertil Steril. 2017 Mar;107(3):521-522.

Introduction: A focus on the medical management of endometriosis.

Casper RF¹.

 

Abstract

In this views and reviews series of articles, we focus on the long-term medical management of endometriosis in lieu of surgery. The development of noninvasive biomarkers will facilitate the early diagnosis of endometriosis and early medical management. We discuss the use of oral progestin-only as first line treatment in place of oral contraceptives. Future medical treatments may be curative rather than simply suppressive or palliative. The section on surgery mainly pertains to failed medical management or specific types of endometriosis which require surgical excision.

 

 

Fertil Steril. 2017 Mar;107(3):699-706.e6.

Endometriosis is associated with aberrant metabolite profiles in plasma.

Letsiou S¹, Peterse DP², Fassbender A², Hendriks MM³, van den Broek NJ¹, Berger R³, O DF², Vanhie A², Vodolazkaia A², Van Langendonckt A⁴, Donnez J⁴, Harms AC⁵, Vreeken RJ⁶, Groothuis PG⁷, Dolmans MM⁴, Brenkman AB¹, D’Hooghe TM⁸.

Abstract

OBJECTIVE:

To identify metabolites that are associated with and predict the presence of endometriosis.

DESIGN:

Metabolomics study using state-of-the-art mass spectrometry approaches.

SETTING:

University hospital and universities.

PATIENT(S):

Twenty-five women with laparoscopically confirmed endometriosis (cases) and 19 women with laparoscopically documented absence of endometriosis (controls). None of the women included in this study had received oral contraception or GnRH agonists for a minimum of 1 month before blood collection.

INTERVENTION(S):

Plasma collection.

MAIN OUTCOME MEASURE(S):

Metabolite profiles were generated and interrogated using multiple mass spectrometry methods, that is, high performance liquid chromatography coupled with negative mode electrospray ionization tandem mass spectrometry, UPLC-MS/MS, and ultra performance liquid chromatography-electroSpray ionization-quadrupole time-of-flight (UPLC-ESI-Q-TOF). Metabolite groups investigated included phospholipids, glycerophospholipids, ether-phospholipids, cholesterol-esters, triacylglycerol, sphingolipids, free fatty acids, steroids, eicosanoids, and acylcarnitines.

RESULT(S):

A panel of acylcarnitines predicted the presence of endometriosis with 88.9% specificity and 81.5% sensitivity in human plasma, with a positive predictive value of 75%. However, due to data limitations the outcome of the receiver operating characteristic curve analysis was not significant.

CONCLUSION(S):

A diagnostic model based on acylcarnitines has the potential to predict the presence and stage of endometriosis.

 

 

Mol Med Rep. 2017 Apr;15(4):2255-2260.

Immunosuppressive macrophages induced by IDO1 promote the growth of endometrial stromal cells in endometriosis.

Mei J¹, Chang KK², Sun HX¹.

 

Abstract

It was previously demonstrated that anomalous expression of indoleamine 2,3-dioxygenase-1 (IDO1) in endometrial stromal cells (ESCs) stimulated an inflammatory response that subsequently initiated the activation of immunosuppressive macrophages in endometriosis. The aim of the present study was to clarify the effect of IDO1‑induced macrophages on the growth of ESCs in endometriosis. Normal ESCs, ectopic ESCs and normal ESCs treated with plasmid pEGFP‑N1‑IDO1 or SD11‑IDO1 short hairpin RNA were co‑cultured with peripheral blood‑derived monocyte (PBMC)‑driven macrophages directly for 48 h. Compared with normal ESCs, the PBMC‑driven macrophages that were co‑cultured with ectopic ESCs displayed a lower phagocytic ability. pEGFP‑N1‑IDO1 transfection of normal ESCs also decreased the phagocytic ability of co‑cultured macrophages. Additionally, pEGFP‑N1‑IDO1‑transfected ESC‑induced macrophages significantly increased the viability and proliferation of ESCs, while ESC apoptosis was decreased, compared with control ESCs. In conclusion, IDO1 educated-macrophages may facilitate the survival of retrograde endometrial tissues, and be involved in the pathogenesis of endometriosis.

 

 

 

 

 

Minerva Ginecol. 2017 Oct;69(5):488-503.

Is there a role for single-port laparoscopy in the treatment of endometriosis?

Daniilidis A¹, Chatzistamatiou K², Assimakopoulos E².

 

Abstract

Endometriosis is among the most common benign gynecological conditions, and it affects 6-15% of women of reproductive. During recent decades, minimally invasive surgical techniques, and especially laparoscopy, have gained significant ground concerning the treatment of gynecological disorders. To date, laparoscopy is considered the gold standard for the diagnosis and treatment of endometriosis. Available English-language papers in PubMed and Scopus databases have been used for the current narrative review. Data from all relevant literature regarding single-port laparoscopy and treatment of endometriosis have been extracted. The main key words used by the authors for the search were: single-port laparoscopy, endometriosis and laparoscopy. Two authors (A.D. and K.C.) performed the data base search and extraction of relevant studies, and a third author (E.A.) consented to the study selection of the 23 relevant papers, consulted and approved the final presentation of the results and conclusions. To date, the laparo-endoscopic single-site surgery (LESS) technique has been used for a variety of procedures in gynecology as well as for a variety of diagnoses. Thus, adhesiolysis, ovarian endometrioma enucleation and salpingo-oophorectomy can be easily performed using the LESS approach. Novel single-site trocars as well as appropriate curved instruments are being designed and produced to facilitate the surgeon utilizing such a demanding technique. However, single-site surgery does not seem to have a place to date in the treatment of deep infiltrating endometriosis due to the complicated surgical maneuvers required for the treatment of this condition combined with technical difficulties posed by the loss of triangulation, and the instrument crowding when LESS is implemented. Apart from being feasible, LESS has also proven to be non-inferior in terms of surgical safety and efficacy, and according to most, but not all, reports, better in terms of cosmetics and postoperative body image perception. Currently, it has been shown that most of the gynecologic operations are feasible using the LESS approach. So, this approach has a role to play in the treatment of endometriosis too, especially concerning the most common manifestations of the disease. However, more extensive research is required to properly evaluate single-port access techniques to conventional minimally invasive ones in the treatment of the different manifestations of endometriosis, concerning short term as well as long term outcomes of the treatment, including the ones associated to fertility.

 

 

Turk J Med Sci. 2017 Feb 27;47(1):115-122.

Endometriosis-associated changes in serum levels of interferons and chemokines.

Măluțan AM¹, Drugan T², Ciortea R¹, Bucuri C¹, Rada MP¹, Mihu D¹.

Abstract

BACKGROUND/AIM:

The aim of the study was to evaluate the serum concentration of main chemokines and interferons in patients with diagnosed endometriosis.

MATERIALS AND METHODS:

A total of 160 women were divided in two study groups (group 1 – endometriosis; group 2 – healthy women). Serum levels of IFN-α, IFN-γ, MCP-1, MIP-1α, MIP-1β, RANTES, eotaxin, IL-8, MIG, IP-10, and IL-17A were measured with Human Multiplex Cytokine Panels. Results. Serum levels of IFN-γ, MCP-1, and IL-8 were significantly higher (mean 14.03, 57.24, and 534.24, respectively, compared to 0.58, 20.51, and 259.82, respectively), and serum levels of IP-10 and eotaxin were significantly lower in women with endometriosiscompared to the controls (mean 1.15 and 1.01, respectively, compared to 3.90 and 3.22, respectively). Conclusions. According to our results women with endometriosis have elevated levels IFN-γ, MCP-1, and IL-8, and lower serum levels of IP-10 and eotaxin, indicating unbalanced immune activity in endometriosis.

 

 

Nutrients. 2017 Feb 28;9(3)

Anti-Endometriotic Effects of Pueraria Flower Extract  in Human Endometriotic Cells and Mice.

Kim JH^1,2, Woo JH³, Kim HM², Oh MS^1,2, Jang DS^1,2, Choi JH^4,5.

 

Abstract

Pueraria flowers have been used as a vegetable and an ingredient for tea and jelly. In this study, we investigated the effects of Pueraria flower extract (PFE) on endometriosis, a common gynaecological disease characterised by local sterile inflammation of peritoneal cavity. PFE suppressed the adhesion of human endometriotic cells 11Z and 12Z to human mesothelial Met5A cells. In addition, PFE significantly inhibited the migration of 11Z and 12Z cells as shown by woundhealing and transwell migration assays. PFE reduced the protein and mRNA levels of matrix metalloproteinase (MMP)-2 and MMP-9 in endometriotic cells. Moreover, extracellular signalregulated kinase (ERK)1/2 was activated by PFE treatment, and an ERK1/2 inhibitor, PD98059, significantly inhibited PFE-inhibited cell migration in endometriotic cells. Furthermore, PFE significantly suppressed endometriotic lesion formation in a mouse model. These data suggest that Pueraria flower is a potential anti-endometriotic agent for the inhibition of endometriotic cell adhesion, migration, and MMP expression.

 

 

Gynecol Endocrinol. 2017 Jul;33(7):534-539.

Postoperative desogestrel for pelvic endometriosis-related pain: a randomized controlled trial.

Tanmahasamut P¹, Saejong R¹, Rattanachaiyanont M¹, Angsuwathana S¹, Techatraisak K¹, Sanga-Areekul N¹.

Abstract

OBJECTIVE:

To determine the effectiveness of desogestrel for relieving endometriosis-related pain.

METHODS:

A double-blinded randomized placebo-controlled trial was conducted in 40 patients who had endometriosis with moderate-to-severe dysmenorrhea or chronic pelvic pain undergoing laparoscopic conservative surgery. After surgery, patients were randomized to desogestrel or placebo group. Outcomes included changes in visual analog scale (VAS) of dysmenorrhea, pelvic pain and dyspareunia, patient satisfaction, and adverse effects.

RESULTS:

Forty patients were randomized to desogestrel group (n = 20) and placebo group (n = 20). At month 6, the desogestrel group had significantly lower median VAS of overall pelvic pain, dysmenorrhea and noncyclic pelvic pain. Comparing with the placebo group, the desogestrel group had greater reduction in VAS of overall pain, dysmenorrhea and pelvic pain, but comparable reduction in VAS of dyspareunia. No patient in the desogestrel group but 4 patients in the placebo group still had moderate-to-severe pelvic pain at 6 months postoperatively. The proportion of patients who rated the treatment as very satisfied was higher in the desogestrel group than in the placebo group. There was no serious adverse event during the study period.

CONCLUSIONS:

Desogestrel is effective and acceptable for postoperative therapy for patients with moderate-to-severe pain related to endometriosis.

 

 

Gynecol Endocrinol. 2017 Jul;33(7):540-543.

Frozen embryo transfer cycles in women with deep endometriosis.

Queiroz Vaz G^1,2, Evangelista AV^1,2, Almeida Cardoso MC², Gallo P^1,2, Erthal MC², Pinho Oliveira MA¹.

Abstract

OBJECTIVE:

To compare the transfer pregnancy rates with frozen embryos from patients with deep endometriosis and non-endometriosis patients.

METHODS:

We conducted a retrospective cohort study of review of medical records of 181 women aged 18-40 years, undergoing transfer of frozen embryos into a fertility center. The data collected was from January 2007 to December 2013.

RESULTS:

Regarding the patients with endometriosis, there was no statistical difference in proportion to compare polycystic ovarian syndrome, male factor, tubal factor and unexplained infertility.

CONCLUSION:

There was no difference between pregnancy rates obtained from frozen embryo transfer in deep endometriosis compared to other causes of infertility.

 

 

J Minim Invasive Gynecol. 2017 Sep – Oct;24(6):896.

The Retroperitoneal Approach to Endometriosis.

Gingold JA¹, Falcone T².

Abstract

STUDY OBJECTIVE:

To demonstrate principles of laparoscopic management of deeply infiltrating endometriosisrequiring retroperitoneal entry.

DESIGN:

Step-by-step demonstration and explanation of technique using videos from patients with deeply infiltrating stage IV endometriosis who failed medical management (Canadian Task Force classification IIIB). This study was exempt from Institutional Review Board review.

SETTING:

Large academic medical center.

INTERVENTIONS:

Laparoscopic surgical excision of endometriosis requiring retroperitoneal dissection.

CONCLUSION:

Surgical excision of endometriosis is an essential tool for the management of symptomatic disease. Chronic inflammation may lead to distorted anatomy and limit the ability to identify pelvic landmarks, precluding the use of blunt dissection. High surgical morbidity may result from unintentional injury to the ureters or retroperitoneal pelvic vessels. Knowledge of pelvic anatomy defines a safe space for sharp entry into the retroperitoneum, ureterolysis using blunt and sharp dissection, identification of pelvic vasculature, and judicious application of electrosurgery. With appropriate technique, the rate of intraoperative complications, including bowel, bladder, and ureteral injury as well as hematoma and bleeding, is approximately 1%. Postoperative complications, including drop in hemoglobin, urinary retention, cystitis, and abdominal wall hematoma, are usually minor, and reoperation rates are well under 1%. Thorough dissection of the retroperitoneum facilitates complete excision of endometriosis with minimum morbidity.

 

 

Gastroenterology Res. 2017 Feb;10(1):59-62.

Colonic Endometriosis: Dig Deeper for Diagnosis.

Badipatla KR¹, Vupputuri A², Niazi M³, Blaise MN¹, Nayudu SK¹.

 

Abstract

Endometriosis is a common gynecological condition wherein there is an ectopic implantation of the uterine endometrial tissue. While several diagnostic modalities are described for the condition, laparoscopy remains the gold standard. There is still an undiscovered area to diagnose colonic endometriosis at an earlier stage. We present a case report of a reproductive age woman with cyclical rectal bleeding diagnosed with colonic endometriosis with colonoscopy and biopsy using saline injection lift and sampling technique. We in our report try to impress the fact that this differential should always be considered in the appropriate clinical setting, especially in women of childbearing age and in such cases, deeper tissue sampling techniques should be sought for, given better diagnostic yield. This may be clinically important given that it may aid in earlier diagnosis and thereby early initiation of appropriate therapy before the disease takes a complicated route. It may also be helpful in avoiding unnecessary surgery, along with the morbidity, complications and costs associated with same.

 

 

Minerva Ginecol. 2017 Jun;69(3):286-294.

Ovarian cancer in endometriosis: an update on the clinical and molecular aspects.

Ruderman R¹, Pavone ME².

 

Abstract

While endometriosis is a benign condition, the presence of endometriosis has been associated with the development of several types of cancers, including ovarian. Endometriomas, or ovarian endometriotic cysts, are found in 17-44% of patients with endometriosis, and may be a common precursor lesions to ovarian cancer. Endometriosis associated ovarian cancer is especially prominent in endometrioid and clear cell ovarian tumor histological subtypes. Several common pathways linking endometriosis and ovarian cancer have been elucidated, including the dominance of certain cytokines, oxidative stress, and a hyper-estrogenic hormonal milieu, which propagate both endometriosis and endometriosis associated ovarian cancer. Additionally, genetic mutations including PTEN, PIK3CA, ARID1A, Wnt/β-catenin, microsatellite instability, Src, and KRAS have been shown to be critical in the pathogenesis of endometriosis associated ovarian cancers. Research continues to develop and provide insights into various prevention, screening, and treatment modalities. In this article, we present a comprehensive review of our current knowledge on this topic in both a clinical and molecular context.

 

 

Minerva Ginecol. 2017 Oct;69(5):504-516.

The role of robotics in the management of endometriosis.

Cela V¹, Obino ME², Sergiampietri C¹, Simi G¹, Papini F¹, Pinelli S¹, Freschi L¹, Artini P¹.

 

Abstract

The advent of robot-assisted laparoscopy (RAL) is an important innovation which has provided new perspectives for the treatment of endometriosis, and particularly of deep infiltrating endometriosis (DIE). RAL offers several technical advantages in the treatment of this complex disease, such as 3D view, tremor filtration and better surgical ergonomics, thus improving surgical performances without no increase in surgical time, blood loss, and intra- or postoperative complications, while also reducing the rate of conversion to laparotomy. Additionally, thanks to its reduced learning curve compared to conventional laparoscopy (CL), it facilitates the training of less experienced surgeons. For these reasons, DIE might be one of the best indications for RAL in gynecologic surgery. However, very few retrospective studies and small cases series, and only one randomized clinical trial have been published in this regard. Further randomized control trials comparing CL to RAL for different stages of endometriosis and different procedures performed are warranted in order to be able to define potential benefits of RAL for endometriosis surgery.

 

 

Minerva Ginecol. 2017 Oct;69(5):462-467.

An update on the biological markers of endometriosis.

Socolov R¹, Socolov D², Sindilar A³, Pavaleanu I¹.

Abstract

INTRODUCTION:

Endometriosis is a disease that affects 7-10% of reproductive-age women. When its diagnosis is delayed, its management becomes more difficult. Both for earlier detection and for therapeutic follow-up, discovering noninvasive biological markers with good specificity for this disease is a promising aspect of its research. We analyzed the recent data in the literature regarding these markers to determine which were worth following.

EVIDENCE ACQUISITION:

This literature review focused on medical data reported in the last 6 years (2011-2016). After identifying articles in PubMed, an analysis of the type of data and level of evidence provided was performed. The selected articles were compared and conclusions regarding the specific markers addressed.

EVIDENCE SYNTHESIS:

Of the 255 articles identified that reported human studies, we had access to the full text for 169 of them. We selected 71 prospective studies to include in our analysis. The studies were divided based on the primary marker studied: 22 analyzed inflammatory and immunological markers, 9 adhesivity and migration markers, 18 genetic polymorphisms, 7 oxidative stress, 4 micro-RNA circulating fragments, and 11 other biological markers (hormonal receptors, leukocytes, and others).

CONCLUSIONS:

CA 125 remains the most recommended marker for suspicion of endometriosis and follow-up. Other markers, such as CA 19-9, CA 72-4, and endometrial cells in peripheral blood, have more value for differentiating endometriosis from other pathologies, while circulating micro-RNA could help clarify the endometrial stem cell’s implication in its pathogeny. Finally, other new urinary markers could be used in early diagnostic and screening strategies.

 

 

Minerva Ginecol. 2017 Oct;69(5):447-461.

Update on endometriosis pathogenesis.

Czyzyk A¹, Podfigurna A¹, Szeliga A², Meczekalski B³.

 

Abstract

Endometriosis is a chronic, inflammatory, condition of high incidence and serious reproductive and general health consequences. Understanding the pathogenesis of endometriosis is crucial for proper diagnostic and ordering the most effective treatment. Even though there is a large body of data regarding this pathology our understanding of the pathogenesis of this disease remains incomplete. The aim of this review is to summarize contemporary data regarding pathogenesis of endometriosis. Current data regarding endometrial origin, metaplastic and Mullerian embryonic rests theory will be reviewed here. Also genetic, epigenetic, environmental factors and immunological dysfunction role in endometriosis will be summarized. To conclude, a lot of effort must be put to integrate the abundant data from genetic, epigenetic and immunological studies to propose one coherent theory for the pathogenesis of endometriosis.

 

 

Gynecol Endocrinol. 2017 Jun;33(6):485-489.

Regulation of endometrial cell proliferation by estrogen-induced BDNF signaling pathway.

Dong F¹, Zhang Q², Kong W², Chen J², Ma J³, Wang L², Wang Y², Liu Y², Li Y², Wen J².

 

Abstract

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin growth factors family. Recent studies indicated that the level of BDNF in follicular fluid is a marker for oocyte quality and infertility. Here, we intend to further investigate the function of BDNF and its signaling pathway in the regulation of endometrial cells proliferation. We found that BDNF is a critical growth factor in endometrial cells. Activation of signal transducer and activator of transcription 3 signaling pathway is required for BNDF-regulated endometrial cell proliferation. Furthermore, BDNF is an effector of estrogen in endometrial cells. Finally, we investigated the different role of Val66Met, a single-nucleotide polymorphism of the BDNF gene, in regulating endometrial cells proliferation. The results showed that BDNF^V66M polymorphism is a loss-of-function polymorphism in the regulation of endometrial cells growth. Given the correlation between endometriosis and infertility, it is important to understand the role of BDNF in regulating endometrial cells proliferation and to develop new therapeutic strategies for the treatment of endometriosis-related infertility.

 

 

Gynecol Endocrinol. 2017 Jun;33(6):429-432.

mir-126 rs4636297 and TGFβRI rs334348 functional gene variants are associated with susceptibility to endometriosis and its severity.

Sepahi N¹, Kohan L^1,2, Jahromi AR³, Daneshbod Y⁴, Hoveidi EN¹.

 

Abstract

microRNAs (miRNAs) are negative regulators in a variety of cellular processes that occur in endometriosis. Therefore, functional polymorphisms in miRNA and miRNA binding sites may affect gene expression and contribute to susceptibility of endometriosis. In this study, we evaluated the association of two miRNA related polymorphisms, mir-126 rs4636297 and TGFβRI rs334348, with endometriosis risk and its severity. This case-control study was done on 157 endometriosis patients and 252 healthy women as a control group. Tetra amplification refractory mutation system-polymerase chain reaction (tetra-ARMS PCR) was designed to determine the polymorphisms. Our finding showed significant differences in genotype frequency of mir-126 rs4636297 between the groups (χ² = 6.26, p = 0.044). A significant protection against endometriosis was found for mir-126 rs4636297 in allele (G versus A allele: OR = 0.695, 95% CI = 0.519-0.931, p = 0.015) and genotype (GG versus AA genotype: OR = 0.451, 95%CI = 0.233-0.873, p = 0.018). Significant association was also observed between the A allele and severity of endometriosis (OR = 0.478, 95%CI = 0.297-0.768, p = 0.002). Moreover, we found a significant association between AA genotype with the risk of endometriosis (OR = 0.493, 95%CI = 0.250-0.970, p = 0.041) and its severity (OR = 0.240, 95%CI = 0.065-0.883, p = 0.032) regarding TGFβRI rs334348 polymorphism. These finding suggest that, for the first time, mir-126 rs4636297 and TGFβRI rs334348 polymorphisms may influence individual’s susceptibility to endometriosis and its severity.

 

 

Int J Gynecol Pathol. 2018 Jan;37(1):88-92.

Clear Cell Carcinoma of the Uterine Cervix Presented as Submucosal Tumor Arising From a Background of Cervical Endometriosis.

Hashiguchi M¹, Kai K, Nishiyama S, Nakao Y, Yokoyama M, Aishima S.

 

Abstract

Clear cell carcinoma (CCC) of the uterine cervix without prenatal diethylstilbestrol exposure is rare, and its etiology is unclear. We present a case of cervical CCC presenting as a submucosal tumor, which strongly suggests an association between cervical endometriosis and cervical CCC. A 56-year-old postmenopausal Japanese woman visited a gynecologic clinic with a complaint of watery vaginal discharge. A few atypical cells suggesting adenocarcinoma were detected in a cervical cytologic specimen. Magnetic resonance imaging revealed a cystic lesion with a solid component at the uterine cervix. Under a tentative diagnosis of cervical cancer, surgery was performed. Although a freshly resected specimen initially showed no tumorous lesion in the cervical mucosa, cutting of the mucosa revealed a solid tumor with a final diagnosis of CCC. The findings of aggregation of hemosiderin-laden macrophages and ectopic endometrium adjacent to the tumor strongly suggest that this tumor arose from cervical endometriosis.

 

 

Appl Immunohistochem Mol Morphol. 2017 Mar;25(3):e21-e24.

Endometrioid Adenocarcinoma Arising in a Paratubal Cyst: A Case Report and Review of the Literature.

Chang C¹, Matsuo K, Mhawech-Fauceglia P.

 

Abstract

A 56-year-old G3P3 postmenopausal woman presented with a 5 month history of abnormal uterine bleeding and pelvic pain. A computed tomographic scan revealed a 5 cm right adnexal cystic mass in addition to a thickened, heterogenous endometrium and leiomyomatous uterus. A total laparascopic hysterectomy and bilateral salpingo-oophorectomy with omental and peritoneal biopsy were performed. Gross examination revealed a 12 week size uterus with small fibroids, normal bilateral atrophic ovaries, and a right paratubal cyst. A 4 cm vegetating mass was found in the right side of the uterine wall. Microscopically, the uterine mass was diagnosed as an endometrioid adenocarcinoma (EAC) FIGO 1 with 70% of myometrial invasion. The remaining endometrium showed a complex atypical hyperplasia. In addition, a 5 cm paratubal cystic mass was found that was separate from the uterus and the right adnexa. The cyst content was a chocolate brown fluid and the cyst wall was smooth with a single solid mass of 2 cm in size. The diagnosis of EAC, FIGO 1 was given. The remaining cyst lining showed endometriotic cyst and foci of endometriosis in the cyst wall. There was no lymphovascular invasion. The entire fallopian tube and ovaries were submitted and they were free of tumor. The patient was diagnosed with primary EAC of the paratubal cyst in addition to EAC of the uterine corpus (pT1b). A close follow-up was recommended. Because of our limited knowledge of carcinomas arising in the paratubal cyst, we will review the literature and discuss their clinical aspects, management, and behavior.

 

 

Acupunct Med. 2017 Jun;35(3):189-199.

Prevalence and factors associated with the use of acupuncture and Chinese medicine: results of a nationally representative survey of 17161 Australian women.

Yang L¹, Adams J¹, Sibbritt D¹.

Abstract

BACKGROUND:

Traditional Chinese Medicine has considerable public support in Australia and elsewhere around the world; the literature suggests Chinese medicine (CM) and acupuncture are particularly popular.

AIM:

To examine factors associated with CM/acupuncture use among young/middle-aged Australian women.

METHODS:

This research formed part of the Australian Longitudinal Study on Women’s Health (ALSWH), a population-based cohort study. Data were obtained from the ‘young’ (34-39 years; n=8010) and ‘middle-aged’ (62-67 years; n=9151) ALSWH cohorts, who completed survey 6 (in 2012) and survey 7 (in 2013), respectively. Outcome measures included use of CM and visits to an acupuncturist in the previous 12 months. Predictive factors included demographic characteristics, and measures of health status (diagnosed chronic medical conditions) and health service utilisation. Statistical analyses included bivariate χ² tests, two proportions Z-tests and backward stepwise multiple logistic regression modelling.

RESULTS:

In total, 9.5% and 6.2% of women in the young and middle-aged cohorts, respectively, had consulted an acupuncturist, and 5.7% and 4.0%, respectively, had used CM. Young women with low iron levels and/or endometriosis were more likely to use CM and/or acupuncture. Middle-aged women with low iron levels and/or chronic fatigue syndrome (CFS) were more likely to use CM, while middle-aged women with arthritis and/or CFS were more likely to use acupuncture.

CONCLUSIONS:

Women with chronic conditions (including arthritis, low iron, CFS and endometriosis) were associated with higher odds of CM/acupuncture use. There is a need for further research to examine the potential benefits of CM/acupuncture for these chronic illnesses.

 

 

Int J Reprod Biomed (Yazd). 2017 Jan;15(1):21-32.

Evaluation of two endometriosis models by transplantation of human endometrial tissue fragments and human endometrial mesenchymal cells.

Jafarabadi M¹, Salehnia M², Sadafi R².

Abstract

BACKGROUND:

The animal models of endometriosis could be a valuable alternative tool for clarifying the etiology of endometriosis.

OBJECTIVE:

In this study two endometriosis models at the morphological and molecular levels was evaluated and compared.

MATERIALS AND METHODS:

The human endometrial tissues were cut into small fragments then they were randomly considered for transplantation into γ irradiated mice as model A; or they were isolated and cultured up to fourth passages. 2×10⁶ cultured stromal cells were transplanted into γ irradiated mice subcutaneously as model B. twenty days later the ectopic tissues in both models were studied morphologically by Periodic acid-Schiff and hematoxylin and eosin staining. The expression of osteopontin (OPN) and matrix metalloproteinase 2 (MMP2) genes were also assessed using real time RT-PCR. 17-β estradiol levels of mice sera were compared before and after transplantation.

RESULTS:

The endometrial like glands and stromal cells were formed in the implanted subcutaneous tissue of both endometriosis models. The gland sections per cubic millimeter, the expression of OPN and MMP2 genes and the level of 17-β estradiol were higher in model B than model A (p=0.03).

CONCLUSION:

Our observation demonstrated that endometrial mesenchymal stromal cells showed more efficiency to establish endometriosis model than human endometrial tissue fragments.

 

 

Sci Rep. 2017 Mar 10;7:44169.

EP2 receptor antagonism reduces peripheral and central hyperalgesia in a preclinical mouse model of endometriosis.

Greaves E¹, Horne AW¹, Jerina H², Mikolajczak M², Hilferty L¹, Mitchell R², Fleetwood-Walker SM², Saunders PT³.

 

Abstract

Endometriosis is an incurable gynecological disorder characterized by debilitating pain and the establishment of innervated endometriosis lesions outside the uterus. In a preclinical mouse model of endometriosis we demonstrated overexpression of the PGE₂-signaling pathway (including COX-2, EP₂, EP₄) in endometriosislesions, dorsal root ganglia (DRG), spinal cord, thalamus and forebrain. TRPV1, a PGE₂-regulated channel in nociceptive neurons was also increased in the DRG. These findings support the concept that an amplification process occurs along the pain neuroaxis in endometriosis. We then tested TRPV1, EP₂, and EP₄ receptor antagonists: The EP₂ antagonist was the most efficient analgesic, reducing primary hyperalgesia by 80% and secondary hyperalgesia by 40%. In this study we demonstrate reversible peripheral and central hyperalgesia in mice with induced endometriosis.

 

 

PLoS One. 2017 Mar 10;12(3):e0173452.

Biomathematical pattern of EMG signal propagation in smooth muscle of the non-pregnant porcine uterus.

Domino M¹, Pawlinski B¹, Gajewski Z¹.

 

Abstract

Uterine contractions are generated by myometrial smooth muscle cells (SMCs) that comprise most of the myometrial layer of the uterine wall. Aberrant uterine motility (i.e., hypo- or hyper-contractility or asynchronous contractions) has been implicated in the pathogenesis of infertility due to the failure of implantation, endometriosisand abnormal estrous cycles. The mechanism whereby the non-pregnant uterus initiates spontaneous contractions remains poorly understood. The aim of the present study was to employ linear synchronization measures for analyzing the pattern of EMG signal propagation (direction and speed) in smooth muscles of the non-pregnant porcine uterus in vivo using telemetry recording system. It has been revealed that the EMG signal conduction in the uterine wall of the non-pregnant sow does not occur at random but it rather exhibits specific directions and speed. All detectable EMG signals moved along the uterine horn in both cervico-tubal and tubo-cervical directions. The signal migration speed could be divided into the three main types or categories: i. slow basic migration rhythm (SBMR); ii. rapid basic migration rhythm (RBMR); and iii. rapid accessory migration rhythm (RAMR). In conclusion, the EMG signal propagation in smooth muscles of the porcine uterus in vivo can be assessed using a linear synchronization model. Physiological pattern of the uterine contractile activity determined in this study provides a basis for future investigations of normal and pathologicall myogenic function of the uterus.

 

 

 

Trials. 2017 Mar 11;18(1):121.

Preventing recurrence of endometriosis by means of long-acting progestogen therapy (PRE-EMPT): report of an internal pilot, multi-arm, randomised controlled trial incorporating flexible entry design and adaption of design based on feasibility of recruitment.

Middleton LJ¹, Daniels JP², Weckesser A³, Bhattacharya S⁴; PRE-EMPT trial collaborative group.

Abstract

BACKGROUND:

Endometriosis is associated with the growth of endometrium in ectopic sites mainly within the pelvis. This results in inflammation and scarring, causing pain and impaired quality of life. Endometriotic lesions can be excised or ablated surgically, but the risk of recurrence is high. A Heath Technology Assessment commissioning call in 2011 sought applications for trials aimed at evaluating long-term effectiveness of postoperative, long-acting, reversible contraceptives (LARCs) in preventing recurrence of endometriosis. A survey of gynaecologists indicated that there was no consensus about which LARC (Levonorgestrel Intrauterine System (LNG-IUS) or depot medroxyprogesterone acetate injection (DMPA)) or comparator (combined oral contraceptive pill (COCP) or no treatment) should be evaluated. Hence, we designed a ‘flexible-entry’ internal pilot to assess whether a four-arm trial was feasible including a possible design adaption based on pilot findings.

METHODS:

In this pilot, women could be randomised to two, three or four treatment options provided that one was a LARC and one was a non-LARC. An assessment of feasibility based on recruitment to these options and a revised substantive trial design was considered by an independent oversight committee.

RESULTS:

The study ran for 1 year from April 2014 and 77 women were randomised. Only 5 (6%) women accepted randomisation to all groups, with 63 (82%) having a LARC preference and 55 (71%) a non-LARC preference. Four-way and three-way designs were ruled out with a two-way LARC versus COCP design, stratified by prerandomisation choice of LARC and optional subrandomisation to LNG-IUS versus DMPA considered a feasible substantive study.

CONCLUSIONS:

Multi-arm studies are potentially efficient as they can answer multiple questions simultaneously but are difficult to recruit to if there are strong patient or clinician preferences. A flexible approach to randomisation in a pilot phase can be used to assess feasibility of such studies and modify a trial design based on chosen recruitment options, but trialists should consider carefully any practical arrangements should groups need to be dropped during a study.

 

 

Clin Radiol. 2017 Jul;72(7):612.e7-612.e15.

MRI in the evaluation of obstructive reproductive tract anomalies in paediatric patients.

Zhang H¹, Qu H², Ning G³, Cheng B³, Jia F³, Li X³, Chen X³.

Abstract

AIM:

To outline the anatomical variations of obstructive reproductive tract anomalies (ORTA) using magnetic resonance imaging (MRI) and its role in preoperative evaluation.

MATERIALS AND METHODS:

MRI and treatment of 21 paediatric patients with ORTA were reviewed and analysed. MRI findings were correlated with ultrasound and surgical findings.

RESULTS:

Patients presented in two distinct ways: primary amenorrhoea with cyclic pelvic pain, or progressive dysmenorrhoea. MRI showed haematocolpos, haematocervix, haematometra, and/or haematosalpinx; it also provided detailed information regarding uterine morphology, ipsilateral kidney absence, and endometriosis. Diagnosis at MRI of the obstruction sites correlated completely (100%) with the surgical diagnosis. Obstruction occurred at different levels of the genital tract, and surgical treatment was given based on the obstruction sites. One patient underwent excision of the hymen tissue for imperforate hymen. Four cases of lower vaginal atresia were treated with vaginoplasty. Three patients with typical Herlyn-Werner-Wunderlich (HWW) syndrome underwent resection of the vaginal septum, and one patient with concurrent post-partum placenta increta was treated accordingly; one patient with atypical HWW syndrome had the left uterus resected. There were 11 cases of cervical agenesis or cervicovaginal dysgenesis, eight of which were complicated with uterine anomalies, and in all cases the uterus was removed. Among the 10 obstructive cervical anomalies, there were three cases of cervical agenesis and seven cases of cervical dysgenesis, including five obliterated cervical os (cervical obstruction), one cervical fibrous cord, and one cervical fragmentation.

CONCLUSION:

ORTA can occur from the hymen to the lower segment of the uterus and requires surgical intervention. The preoperative evaluation is vital to guide proper surgery. MRI, with its imaging advantages, is the imaging technique of choice to assess the obstructed sites and complicated anomalies of ORTA.

 

 

Environ Int. 2017 May;102:207-212.

Perfluoroalkyl substances and endometriosis-related infertility in Chinese women.

Wang B¹, Zhang R², Jin F³, Lou H³, Mao Y³, Zhu W⁴, Zhou W¹, Zhang P², Zhang J⁵.

 

Abstract

Endometriosis is one of the main causes for female infertility. Previous studies suggested that perfluoroalkyl substances (PFASs), a group of ubiquitous environmental chemicals with properties of endocrine disruption and reproductive toxicity, were risk factors for endometriosis but there lacks direct evidence on the possible role of PFASs in endometriosis-related infertility. To fill this gap, we examined the association between PFASs and endometriosis-related infertility among Chinese reproductive-age women in a case-control study, which comprised 157 surgically confirmed endometriosis cases and 178 controls seeking infertility treatment because of male reproductive dysfunction in 2014 and 2015. Blood specimens were collected at the enrollment and analyzed for ten PFASs. Logistic regression was utilized to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) for individual PFAS compound. Plasma concentrations of perfluorobutane sulfonic acid (PFBS) were associated with an increased risk of endometriosis-related infertility (second vs. lowest tertile: OR=3.74, 95% CI: 2.04, 6.84; highest vs. lowest tertile: OR=3.04, 95% CI: 1.65, 5.57). This association remained consistent when we restricted to subjects with no previous pregnancy (second vs. lowest tertile: OR=2.91, 95% CI: 1.28, 6.61; highest vs. lowest tertile: OR=3.41, 95% CI: 1.52, 7.65) or to subjects without other gynecologic pathology (second vs. lowest tertile: OR=4.65, 95% CI: 2.21, 9.82; highest vs. lowest tertile: OR=3.36, 95% CI: 1.58, 7.15). Plasma concentrations of perfluoroheptanoic acid (PFHpA), perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) were inversely associated with endometriosis-related infertility, but the associations were attenuated in the sensitivity analyses. Our preliminary evidence suggests that exposure to PFBS may increase the risk of female infertility due to endometriosis. Future prospective studies are necessary to confirm these findings.

 

 

Reprod Sci. 2017 Jul;24(7):989-995.

Cigarette Smoking Affects Uterine Receptivity Markers.

Sahin Ersoy G¹, Zhou Y¹, İnan H², Taner CE², Cosar E¹, Taylor HS¹.

Abstract

OBJECTIVE:

Smoking negatively affects fertility and the rate of other endometrial diseases. To determine the effect of smoking on endometrial physiology, we evaluated 2 endometrial regulatory cytokines and receptivity markers, C-X-C motif chemokine ligand 12 (CXCL12) and fibroblast growth factor 2 (FGF2), both in vitro and in vivo.

STUDY DESIGN:

The human endometrial stromal cell line (HESC) and primary human endometrial stromal cells were treated with cigarette smoking extract (CSE) or with vehicle control. Twenty female mice were randomly assigned to either cigarette smoke (CS) exposure for 8 weeks or to a nonsmoke (NS) group that received room air. Immunohistochemical analysis of CXCL12 and FGF2 expression was performed in mouse uterine tissue. Human endometrial samples were obtained from both nonsmokers and smokers. Real-time reverse transcription-polymerase chain reaction was performed for all cell cultures and human samples.

RESULTS:

Compared to controls, CXCL12 and FGF2 mRNA expression were significantly decreased in CSE-exposed HESC and primary cells. In mice, immunohistochemical analysis showed that both CXCL12 and FGF2 protein expression was lower in the CS group compared to controls. Similarly, both CXCL12 and FGF2 expression were decreased in women who smoke compared to nonsmokers.

CONCLUSION:

Decreased endometrial CXCL12 and FGF2 expression contribute to the impaired endometrial receptivity in women who smoke. Smoking is also associated with decreased rates of endometrial cancer and endometriosis; increased CXCL12 and FGF2 are implicated in both conditions. The changes in the expression of cytokines described here may explain the impact of smoking on all of these diseases. Tobacco has direct effects on normal endometrium that impacts endometrial health and disease.

 

 

Pathol Res Pract. 2017 May;213(5):447-452.

Clear cell colorectal carcinoma: Time to clarify diagnosis.

Remo A¹, Grillo F², Mastracci L², Fassan M³, Sina S⁴, Zanella C⁵, Parcesepe P⁴, Damiano Urso E⁶, Pancione M⁷, Bortuzzo G⁵, Scarpa A⁴, Manfrin E⁴.

 

Abstract

Primary clear cell colorectal carcinoma (CCC) is a very rare entity accounting for only 35 cases reported in the Literature. CCC is neither classified as a distinct entity nor is it defined as a CRC variant because its ontogeny remains unclear. Most of the reported CCC were found in the distal colon in patients with a mean age of 56 years. Histologically, clear cell change is the main morphologic feature and may present in a “pure” form, composed exclusively of clear cells, or in a “composite” form, admixed with other morphologically different components. It is possible to distinguish two biologically different types of CCC, with different clinical-pathologic features, therapeutic management and diagnostic criteria: a) Intestinal CCC consisting of an aggressive neoplasm, affecting mainly adult men, characterized by an intestinal-type immunoprofile (CK20+, CK7-, CEA+, CDX-2+) and b) Müllerian CCC consisting of an indolent carcinoma of the sigmoid-rectum, affecting young women, characterized by a different (CK7+, CK20-, CEA-, CA125 +) immunoprofile. Considerable diagnostic difficulties can arise in distinguishing CCC and primary or secondary clear cell neoplasms, such as metastases from renal carcinoma, lower urinary tract, female genital tract, adrenal gland, mesothelioma, melanoma and primary intestinal PEComa. In this paper we review the Literature with two additional cases in order to define the diagnostic criteria of CCC.

 

 

Climacteric. 2017 Apr;20(2):138-143.

Endometriosis after menopause: physiopathology and management of an uncommon condition.

Streuli I¹, Gaitzsch H¹, Wenger JM¹, Petignat P¹.

 

Abstract

Endometriosis is a hormone-dependent inflammatory disease that is usually characterized by infertility and pain symptoms. This disease mainly occurs during the reproductive years and is rarely diagnosed after menopause. We discuss the physiopathology of this condition after menopause as well as treatment options and the risk of malignant transformation. Occurrence or progression of postmenopausal endometriosis lesions could be related to extra-ovarian production of estrogen by endometriosis lesions and adipose tissue, which becomes the major estrogen-producing tissue after menopause. Postmenopausal women with symptomatic endometriosis should be managed surgically because of the risk of malignancy; medical treatments can be used in cases of pain recurrence after surgery. Aromatase inhibitors act by decreasing extra-ovarian estrogen production and by blocking the feed-forward stimulation loop between inflammation and aromatase within endometriosis lesions. The evidence is currently insufficient to support a conclusion about the optimal hormone replacement therapy for women with endometriosis. The question of malignant transformation of endometriosis in response to hormone replacement therapy in women with a history of endometriosis remains unanswered and needs a long-term follow-up study to evaluate the risk of an adverse outcome. Further studies should be performed to determine the optimal management of menopausal women with endometriosis.

 

 

Clin Obstet Gynecol. 2017 Jun;60(2):245-251.

New Developments in Surgery for Endometriosis and Pelvic Pain.

Luu TH¹, Uy-Kroh MJ.

 

Abstract

Endometriosis is a common disease affecting reproductive age women. Pain is one of the most common symptoms associated with endometriosis. When medical therapy has failed or in known deeply infiltrating endometriosis, surgical management is warranted. Laparoscopy is the gold standard for diagnosis and treatment of endometriosis. Recent developments in surgery have shown the feasibility of robotic surgery for endometriosis, although these methods have not been shown to be superior to conventional laparoscopy. Enhanced imaging techniques including fluorescence imaging and narrow band imaging have also been studied. However, long-term clinical benefits have yet to be demonstrated.

 

 

Eur J Obstet Gynecol Reprod Biol. 2017 Apr;211:182-187.

Non-ART pregnancy predictive factors in infertile patients with peritoneal superficial endometriosis.

Boujenah J¹, Cedrin-Durnerin I², Herbemont C³, Sifer C⁴, Poncelet C⁵.

Abstract

OBJECTIVE:

To study the predictive factors for non-ART pregnancy in infertile women after laparoscopic diagnosis and surgery for isolated superficial peritoneal endometriosis (SUP).

STUDY DESIGN:

Retrospective observational study from January-2004 to December-2015 in a tertiary care university hospital and Assisted Reproductive Technology (ART) centre. Infertile women with laparoscopic surgery for SUP (with histologic diagnosis) were included. The surgical treatment was followed by spontaneous fertility or post-operative ovarian stimulation (pOS) using superovulation (gonadotrophins)±Intra Uterine Insemination (IUI). The main outcomes were the non-ART clinical pregnancy rates and its predictive factors.

RESULT(S):

Over the period study, 315 women were included. Of these, 133 (42.3%) women had non-ART pregnancy. The mean time to conceive was 6 months (±6days). Univariate analysis for non-ART pregnancy after surgery showed that: (i) no difference was observed according to age, length of infertility, Body Mass Index (BMI), the rate of previous pregnancy, and the pre-operative ovarian stimulation rate; (ii) diminished ovarian reserve and previous miscarriage were higher in the non-pregnant women group (8.3 versus 19.1%, p<0.05; 3.5% versus 9%, p=0.06, respectively); (iii) the mean EFI score and pOS were higher in pregnant women (7.7 versus 7.2, p=0.02; 49.2% versus 26.7%, p<0.01); and (iv) IUI did not show any benefit for pregnancy (22% after superovulation versus 27.2% after superovulation and IUI). In the multivariate analysis, only pOS (adjusted OR 2.504, 95% CI [1.537-4.077]) and DOR (aOR 0.420, 95% CI [0.198-0.891]) remained significantly associated with the incidence of pregnancy.

CONCLUSION(S):

After laparoscopic surgery for peritoneal superficial endometriosis related infertility, ovarian stimulation improved pregnancy rate, while diminished ovarian reserve had a worse prognosis for pregnancy.

 

 

 

J Neuroinflammation. 2017 Mar 14;14(1):53.

Macrophage and nerve interaction in endometriosis.

Wu J¹, Xie H¹, Yao S², Liang Y³.

 

Abstract

Dysregulation of the immune system in endometriotic milieus has been considered to play a pivotal role in the pathogenesis of endometriosis. Macrophage recruitment and nerve fiber infiltration are the two major characteristics of this aberrant immune environment. First, the recruitment of macrophages and their polarization phenotype within the endometriotic lesion have been demonstrated to facilitate the development and maintenance of endometriosis. M1 phenotype of macrophages has the capacity to secrete multiple cytokines for inflammatory response, while M2 macrophage possesses an opposite property that can mediate the process of immunosuppression and neuroangiogenesis. Upon secretion of multiple abnormal signal molecules by the endometriotic lesion, macrophages could alter their location and phenotype. These changes facilitate the accommodation of the aberrant microenvironment and the exacerbation of disease progression. Second, the infiltration of nerve fibers and their abnormal distribution are proved to be involved in the generation of endometriosis-associated pain and inflammatory response. An imbalance in sensory and sympathetic innervation and the abnormal secretion of different cytokines could mediate neurogenesis and subsequent peripheral neuroinflammation in endometriosis. Although endometriosis creates an inflammatory milieu promoting macrophage infiltration and an imbalanced innervation, interaction between macrophages and nerve fibers in this process remains unknown. The aim of this review is to highlight the role of macrophage and nerve interaction in endometriosis, where macrophage recruitment and neurogenesis can be the underlying mechanism of neuroinflammation and pathogenesis of endometriosis.

 

 

Cancer Causes Control. 2017 May;28(5):371-383

A prospective cohort study of oral contraceptive use and ovarian cancer among women in the United States born from 1947 to 1964.

Shafrir AL^1,2, Schock H³, Poole EM⁴, Terry KL^5,6, Tamimi RM^4,5, Hankinson SE^4,5,7, Rosner BA^4,8, Tworoger SS^4,5.

Abstract

PURPOSE:

Oral contraceptives (OCs) have been consistently associated with a reduced ovarian cancer risk; however, most previous studies included women in older birth cohorts using high-dose OC formulations. We assessed OC use, including type and dose, and ovarian cancer risk among women born between 1947 and 1964 using more recent formulations.

METHODS:

We included 110,929 Nurses’ Health Study II participants. Women reported duration of OC use and brands used from age 13 to baseline (1989) and every 2 years thereafter through 2009. We categorized brands by estrogen and progestin type, dose, and potency, and used Cox proportional hazards models, adjusted for age, calendar time, reproductive factors, and body mass index, to assess associations with ovarian cancer.

RESULTS:

Over 2,178,679 person-years of follow-up, we confirmed 281 cases. At baseline, 83% of participants reported ever using OCs. Compared to never use, we observed an increased risk of ovarian cancer with ≤6 months of OC use (HR 1.82; 95% CI 1.13-2.93) but a non-significant 57% (95% CI 0.18-1.03) decreased risk with ≥15 years of OC use. The increased risk among short-term users (≤1 year) was restricted to OCs containing mestranol (HR 1.83; 95% CI 1.16-2.88) and first-generation progestin (HR 1.72; 95% CI 1.11-2.65).

CONCLUSION:

The associations between OCs and ovarian cancer observed for this younger birth cohort differ substantially from the results of previous cohort studies, possibly reflecting changes in OC formulations and use patterns over time, although these results could be due to chance. Additional studies should evaluate newer OC formulations and ovarian cancer risk.

 

 

Biomark Med. 2017 Apr;11(4):313-317.

Plasma brain-derived neurotrophic factor in women with pelvic pain: a potential biomarker for endometriosis?

Rocha AL¹, Vieira EL², Ferreira MC¹, Maia LM¹, Teixeira AL^2,3, Reis FM¹.

Abstract

AIM:

To test whether plasma BDNF levels are useful to predict the presence of endometriosis in women with pelvic pain.

PATIENTS & METHODS:

Prospective cross-sectional study including 67 consecutive women aged 24-49 years, scheduled for laparoscopy due to chronic pelvic pain. Preoperative plasma samples were assayed for BDNF using a commercial enzyme immunoassay.

RESULTS:

Women with ovarian endometrioma had higher preoperative plasma BDNF (1063 ± 157 pg/ml) compared with women with other benign ovarian tumors (537 ± 131 pg/ml, F = 2.53; p = 0.02). However, plasma BDNF levels were not helpful to indicate the presence of peritoneal or deep infiltrating endometriosis. Plasma BDNF levels were positively correlated with the severity of pelvic pain (r = 0.489; p < 0.0001).

CONCLUSION:

Plasma BDNF might be a biomarker of ovarian endometrioma but not a useful diagnostic marker to detect other forms of endometriosis in women with painful symptoms.