Gynecol Obstet Fertil Senol. 2018 Mar 7. pii: S2468-7189(18)30039-4. doi: 10.1016/j.gofs.2018.02.007. [Epub ahead of print]

Evidence-based ways of colorectal anastomotic complications prevention in the setting of digestive deep endometriosis resection: CNGOF-HAS Endometriosis Guidelines.

Loriau J¹, Petit E², Mephon A³, Angliviel B⁴, Sauvanet E³.

 

Abstract

Management of deep pelvic and digestive endometriosis can lead to colorectal resection and anastomosis. Colorectal anastomosis carries risks for dreaded infectious and functional morbidity. The aim of the study was to establish, regarding the published data, the role of the three most common used surgical techniques to prevent such complications: pelvic drainage, diverting stoma, epiplooplasty. Even if many studies and articles have focused on colorectal anastomotic leakage prevention in rectal cancer surgery data regarding this topic in the setting of endometriosis where lacking. Due to major differences between the two situations, patients, diseases the use of the conclusions from the literature have to be taken with caution. In 4 randomized controlled trials the usefulness of systematic postoperative pelvic drainage hasn’t been demonstrated. As this practice is not systematically recommended in cancer surgery, its interest is not demonstrated after colorectal resection for endometriosis. There is a heavy existing literature supporting systematic diverting stoma creation after low colorectal anastomosis for rectal cancer. Keeping in mind the important differences between the two situations, the conclusions cannot be directly extrapolated. In endometriosis surgery after low rectal resection, stoma creation must be discussed and the patient must be informed and educated about this possibility. Even if widely used there is no data supporting the role of epiplooplasty in colorectal anastomotic complication prevention? The place for epiplooplasty in preventing rectovaginal fistula occurrence in case of concomitant resection hasn’t been studied.

 

 

 

Best Pract Res Clin Obstet Gynaecol. 2018 Feb 15. pii: S1521-6934(18)30032-4. doi: 10.1016/j.bpobgyn.2018.01.014. [Epub ahead of print]

Pathophysiology of endometriosis-associated pain: A review of pelvic and central nervous system mechanisms.

Coxon L¹, Horne AW², Vincent K³.

 

Abstract

Although pain is one of the main symptoms women with endometriosis present with, there is poor correlation between symptom severity and disease burden and the underlying biological mechanisms by which pain arises are still only poorly understood. We briefly review the neurobiology of pain before considering mechanisms that may be specifically relevant in the context of endometriosis. The role of pelvic factors such as new nerve fibre growth, peritoneal fluid and inflammation is explored with a particular focus on studies where these factors have been associated with pain symptoms rather than just being compared between women with endometriosis and disease-free controls. We then consider the role of the central nervous system and associated systems, including the stress axis and psychological factors, in the modulation of pain. The potential for changes in these systems to be a cause and/or a consequence of the pain and how they might explain some of the known associations between endometriosis and other somatic symptoms is discussed. The chapter concludes by considering the implications of these mechanisms on treatment strategies for these women.

 

 

 

Fertil Steril. 2018 Mar 7. pii: S0015-0282(17)32099-X. doi: 10.1016/j.fertnstert.2017.11.029. [Epub ahead of print]

High number of endometrial polyps is a strong predictor of recurrence: findings of a prospective cohort study in reproductive-age women.

Gu F¹, Zhang H², Ruan S³, Li J⁴, Liu X¹, Xu Y⁵, Zhou C⁶.

Abstract

OBJECTIVE:

To compare the incidence of recurrence between a cohort with a high number (≥6) of endometrial polyps (EPs) and a single-EP cohort among reproductive-age patients after polypectomy.

DESIGN:

Prospective observational cohort study.

SETTING:

Single university center.

PATIENT(S):

Premenopausal women who underwent hysteroscopic endometrial polypectomy were recruited.

INTERVENTION(S):

Patients underwent a transvaginal ultrasound scan every 3 months after polypectomy to detect EP recurrence. Kaplan-Meier and Cox regression models were used to compare the risk of recurrence between the two cohorts and analyze the potential risk factors for EP recurrence.

MAIN OUTCOME MEASURE(S):

EP recurrence rate.

RESULT(S):

The study enrolled 101 cases with a high number of EP and 81 cases with a single EP. All baseline parameters were similar except that the high number of EP cohort had a slightly lower mean age than the single EP cohort (33.5 [range 30.0-39.0] vs. 36.0 [30.5-43.0] years). The risk of recurrence in the high number of EP cohort was 4.08 (95% confidence interval [CI] 1.89-8.81) times higher than that in the single-EP cohort 1 year after polypectomy, with a recurrence rate of 45.5% versus 13.4%, respectively. A high number of EPs, endometriosis, and previous polypectomy history were independently associated with polyp recurrence.

CONCLUSION(S):

The high number of EP cohort was much more prone to recurrence than the single-EP cohort. A high number of EPs, endometriosis, and previous polypectomy history were independent risk factors for recurrence. A high number of EPs is suggested to be a distinct subgroup with different pathogenesis, which warrants frequent monitoring and prevention.

Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

 

 

 

BMJ Case Rep. 2018 Mar 9;2018. pii: bcr-2018-224181. doi: 10.1136/bcr-2018-224181.

Rare case of thoracic endometriosis presenting with lung nodules and pneumothorax.

Gates J¹, Sharma A¹, Kumar A^1,2.

 

Abstract

We present the case of a 34-year-old Nigerian woman who was referred to the Respiratory team with a 12-month history of breathlessness. She was concurrently being investigated for an abdominal mass and rectal and vaginal bleeding. Consequently, she underwent cross-sectional imaging of her chest, abdomen and pelvis, revealing a small right-sided pneumothorax and right lower lobe pleural-based lesion. Shortly thereafter, she was admitted to the hospital with chest pain and required chest drain insertion. This partially treated her pneumothorax but she required referral to a cardiothoracic centre for definitive diagnosis and to manage her non-resolving pneumothorax. Biopsies from the video-assisted thoracoscopic surgery confirmed the very rare diagnosis of thoracic endometriosis.

 

 

 

Fertil Steril. 2018 Mar 8. pii: S0015-0282(18)30060-8. doi: 10.1016/j.fertnstert.2018.01.035. [Epub ahead of print]

Introduction: Uterine adenomyosis, another enigmatic disease of our time.

Donnez J¹, Donnez O², Dolmans MM³.

 

Abstract

Like endometriosis, uterine adenomyosis is another enigmatic disease and remains a source of controversy. Uterine adenomyosis is characterized by the presence of endometrial glands in the myometrium. Two main theories may explain its pathogenesis: adenomyosis may arise from invagination of the myometrial basalis into the myometrium; or an alternative theory maintains that it may result from metaplasia of displaced embryonic pluripotent müllerian remants or differentiation of adult stem cells. Uterine adenomyosis is responsible for pelvic pain, abnormal bleeding, and infertility. Its diagnosis may be improved by high quality imaging. In this issue’s Views and Reviews, authors stress the urgent need to establish some systematic classification. Medical and surgical strategies are discussed. It should be emphasized that treatment should be designed according to a patient’s symptoms and an individual’s needs. Surgical treatment remains a matter of debate. Indeed, the risk of uterine rupture during pregnancy after adenomyomectomy is a reality. Therefore, continued research into new molecules based on the pathogenic mechanisms is vital.

 

 

 

Gynecol Obstet Fertil Senol. 2018 Mar 8. pii: S2468-7189(18)30048-5. doi: 10.1016/j.gofs.2018.02.016. [Epub ahead of print]

[Urinary tract involvement by endometriosis. Techniques and outcomes of surgical management: CNGOF-HAS Endometriosis Guidelines].

 

Bolze PA¹, Paparel P², Golfier F³.

 

Abstract

Urinary tract involvement by endometriosis is reported in 1% of endometriosis patients (NP3). Consequences range from pelvic pain for bladder localizations to silent kidney loss in case of chronic ureteral obstruction (NP3). The feasibility of laparoscopic management was widely proven (NP3) and may reduce hospital stay length (NP4). Radical surgery with partial cystectomy for bladder localizations was shown to significantly and durably reduce pain symptoms with low risk of a severe postoperative complications (NP3). Medical hormonal treatment also shows short-term reduction of pain symptoms (NP4). Transureteral resection of bladder endometriosis nodule is not recommended (grade C) because of a high postoperative recurrence rate (NP4). Given a high risk of silent kidney loss, it is recommended that patients with ureteral involvement by endometriosis are managed by a multidisciplinary team considering urinary and potential extra-urinary localizations of endometriosis (grade C). No recommendation can be made on which technique to prefer between conservative (ureterolysis) or radical surgical techniques or on benefit and length of ureteral stents in case of ureteral involvement. Surgical management of bladder and ureteral localizations of endometriosis do not seem to be associated with altered or improved postoperative fertility (NP4). Since late postoperative ureteral anastomosis stenosis were reported with silent kidney loss, repeated postoperative imaging monitoring is justified (expert opinion).

 

 

 

Gynecol Obstet Fertil Senol. 2018 Mar 8. pii: S2468-7189(18)30052-7. doi: 10.1016/j.gofs.2018.02.020. [Epub ahead of print]

Strategies and surgical management of endometriosis: CNGOF-HAS EndometriosisGuidelines.

 

Roman H¹, Ballester M², Loriau J³, Canis M⁴, Bolze PA⁵, Niro J⁶, Ploteau S⁷, Rubod C⁸, Yazbeck C⁹, Collinet P⁸, Rabischong B⁴, Merlot B⁶, Fritel X¹⁰.

 

Abstract

The article presents French guidelines for surgical management of endometriosis. Surgical treatment is recommended for mild to moderate endometriosis, as it decreases pelvic painful complaints and increases the likelihood of postoperative conception in infertile patients (A). Surgery may be proposed in symptomatic patients with ovarian endometriomas which diameter exceeds 20mm. Cystectomy allows for better postoperative pregnancy rates when compared to ablation using bipolar current, as well as for lower recurrences rates when compared to ablation using bipolar current or CO₂ laser. Ablation of ovarian endometriomas using bipolar current is not recommended (B). Surgery may be employed in patients with deep endometriosis infiltrating the colon and the rectum, with good impact on painful complaints and postoperative conception. In these patients, laparoscopic route increases the likelihood of postoperative spontaneous conception when compared to open route. When compared to conservative rectal procedures (shaving or disc excision), segmental colorectal resection increases the risk of postoperative stenosis, requiring additional endoscopic or surgical procedures. In large deep endometriosis infiltrating the rectum (>20mm length of bowel infiltration), conservative rectal procedures do not improve postoperative digestive function when compared to segmental resection. In patients with bowel anastomosis, placing anti-adhesion agents on contact with bowel suture is not recommended, due to higher risk of bowel fistula (C). Various other recommendations are proposed in the text, however, they are based on studies with low level of evidence.

 

 

 

Acta Obstet Gynecol Scand. 2018 Mar 12. doi: 10.1111/aogs.13343. [Epub ahead of print]

Intra- and interobserver variability in nodule size of rectosigmoid endometriosismeasured by two- and three-dimensional transvaginal sonography.

Egekvist AG^1,2, Forman A^1,2, Riiskjaer M^1,2, Kesmodel US^3,4, Mathiasen M^1,2, Seyer-Hansen M^1,2.

Abstract

INTRODUCTION:

The aim of the study was to assess the intra- and interobserver variability of two- and three-dimensional rectosigmoid nodule size measurements by transvaginal ultrasonography in patients with rectosigmoid endometriosis.

MATERIAL AND METHODS:

Intra- and interobserver variability was assessed in 10 and 30 patients, respectively. Measurements in two dimensions were performed in real-time during the scan, and three-dimensional measurements of volume were done on a computer. Differences within and between observers were expressed in absolute units (mm) and percentage (%) of average nodule size. Coefficient of repeatability and Bland-Altman plots with limits of agreement were used to evaluate the intra- and interobserver variability.

RESULTS:

Intra- and interobserver variability in two-dimensional sonography ranged from 11-14 mm or 46-51% for length, 3-6 mm or 32-57% for depth and 5-9 mm or 33-58% for width of the nodule. Results of three-dimensional sonography, with assessment of nodule volume, showed intra- and interobserver variability between 0.4-2.5 times the average nodule size.

CONCLUSIONS:

Measurements of rectosigmoid endometriosis nodule size with two- and three- dimensional transvaginal ultrasonography were associated with large intra- and interobserver variability, and these techniques should therefore be used with caution in clinical control and research of nodule growth. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

 

 

 

Curr Probl Cancer. 2018 Feb 9. pii: S0147-0272(18)30009-6. doi: 10.1016/j.currproblcancer.2018.02.001. [Epub ahead of print]

Primary squamous cell carcinoma arising from endometriosis of the ovary: A case report and literature review.

Xu Y¹, Li L².

 

Abstract

Cases of squamous cell carcinoma (SCC) arising from ovarian endometriosis have been rarely reported. Most of the patients show a poor prognosis and present with a diminished survival time. We present a SCC case arising from endometriosis, and analyzed the clinical, therapeutic, and pathologic features through a comprehensive literature review. A 43-year premenopausal woman (gravida 2, para 1) presented to our hospital due to sudden pain in lower abdomen. Exploratory laparotomy indicated rupture of left ovarian cyst and intra-abdominal hemorrhage were observed. Frozen section pathologic examination indicated malignant ovarian (left-sided) epithelial tumor (poorly differentiated squamous carcinoma). She received hysterectomy, adnexectomy, and omentectomy. Initially, the patient received 3 cycles of chemotherapy using paclitaxel and cisplatin via peritoneal injection. Subsequently, the regimen was altered to 2 cycles of paclitaxel or cisplatin chemotherapy through intravenous injection due to poor tolerance. Upon diagnosis of vaginal metastasis, 2 cycles of chemotherapy was performed using cisplatin, doxorubicin, and cyclophosphamide. Pathologic analysis revealed massive poorly differentiated squamous carcinoma in the fibrous tissues. Besides, cancer embolus was noticed in the lymphatic vessels. Besides our case, 20 cases of infiltrating SCC of the ovary associated with or arising from endometriosis were found. The tumor was associated with 80% patient mortality in the first few months. Adjuvant chemotherapy with paclitaxel and carboplatin or cisplatin appeared to contribute to the survival duration. The best outcomes were obtained in patients received paclitaxel and carboplatin or cisplatin after radical surgery. In future, further studies are needed to validate the efficiency of such regimen.

 

 

 

Best Pract Res Clin Obstet Gynaecol. 2018 Feb 15. pii: S1521-6934(18)30033-6. doi: 10.1016/j.bpobgyn.2018.01.015. [Epub ahead of print]

Medical treatment of endometriosis-related pain.

Vercellini P¹, Buggio L², Frattaruolo MP³, Borghi A⁴, Dridi D⁵, Somigliana E⁶.

 

Abstract

Available medical treatments for symptomatic endometriosis act by inhibiting ovulation, reducing serum oestradiol levels, and suppressing uterine blood flows. For this, several drugs can be used with a similar magnitude of effect, in terms of pain relief, independently of the mechanism of action. Conversely, safety, tolerability, and cost differ. Medications for endometriosis can be categorized into low-cost drugs including oral contraceptives (OCs) and most progestogens, and high-cost drugs including dienogest and GnRH agonists. As the individual response to different drugs is variable, a stepwise approach is suggested, starting with OCs or low-cost progestogens, and stepping up to high-cost drugs only in case of inefficacy or intolerance. OCs may be used in women with dysmenorrhea as their main complaint, and when only superficial peritoneal implants or ovarian endometriomas <5 cm are present, while progestogens should be preferred in women with severe deep dyspareunia and when infiltrating lesions are identified.

 

 

 

Best Pract Res Clin Obstet Gynaecol. 2018 Feb 8. pii: S1521-6934(18)30025-7. doi: 10.1016/j.bpobgyn.2018.01.007. [Epub ahead of print]

The significance and evolution of menstruation.

Jarrell J¹.

 

Abstract

Historically, the evolutionary origins of menstruation have been based on two theories: the ability to eliminate infectious agents carried to the uterus with spermatozoa and the comparative conservation of energy with menstruation compared to its absence. In the menstruating species, more recent theories have identified spontaneous decidualization as the key adaptive mechanism. Spontaneous decidualization is seen as a mechanism to provide the mother with protection from the invasive characteristics of the embryo. Physiologically, menstruation involves complex interactions of inflammation and vascular mechanisms to stabilize the endometrium and allow a regulated loss of endometrial tissues and blood. A variety of human illnesses can be better understood as vulnerabilities associated with these evolutionary developments, including recurrent pregnancy loss, placenta accreta, ectopic pregnancy, endometriosis, adenomyosis, dysmenorrhea, and chronic pelvic pain. While the evolutionary aspects of these diseases indicate why such illnesses can occur, in some instances, they also provide a basis for treatment, prevention and future research direction.

 

 

 

Gynecol Obstet Fertil Senol. 2018 Mar 9. pii: S2468-7189(18)30033-3. doi: 10.1016/j.gofs.2018.02.001. [Epub ahead of print]

Extragenital endometriosis: Parietal, thoracic, diaphragmatic and nervous lesions. CNGOF-HAS Endometriosis Guidelines.

Merlot B¹, Ploteau S², Abergel A³, Rubob C⁴, Hocke C⁵, Canis M⁶, Fritel X⁷, Roman H⁸, Collinet P⁴.

Abstract

According to some studies, extragenital endometriosis represents 5% of the localisations. Its prevalence seems to be underestimated. The extra pelvic localisation can make the diagnosis more difficult. Nevertheless, the recurrent and catamenial symptomatology can evoke this pathology. Surgery seems to be the unique efficient treatment for parietal lesions. Pain linked to nervous lesions (peripheric and sacral roots) seems to be underestimated and difficult to diagnose because of various localisations. Neurolysis seems to have encouraging results. Diaphragmatic lesions are often discovered either incidentally during laparoscopy, or by pulmonary symptomatology as recurrent catamenial pneumothorax or cyclic thoracic pain. Surgical treatment seems as well to be efficient.

 

 

 

Gynecol Obstet Fertil Senol. 2018 Mar 9. pii: S2468-7189(18)30037-0. doi: 10.1016/j.gofs.2018.02.005.

Expectations of women with endometriosis: What information to deliver? CNGOF-HAS Endometriosis Guidelines.

Denouel A¹, Fauconnier A², Torre A³.

 

Abstract

Women with endometriosis often say that the information doctors give them should be improved. Patient support groups can provide missing information but may lack objectivity, or reliability, and may even generate anxiety or even harm their health. Clear unbiased medical information is the ideal. New patients with endometriosis wish to be taken seriously by primary care physicians, and be referred quickly to a specialist without further unnecessary investigation or delay. The diagnosis of endometriosis should ideally be made quickly, and should clearly specify the nature of the disease, its evolution, and its consequences on quality of life, relationships, and fertility. When choosing a treatment, information should state the risks of each treatment, the risks of recurrence long term, and the therapeutic alternatives. These should include conventional medical treatment, lifestyle adaptation, or alternative therapies. In case of surgery, prior written information should be provided, the likely scar appearance, the short and long term consequences in terms of pain, postoperative recovery time and complication rates. Once the surgery is performed, the degree of endometriotic involvement and the treatment undertaken should be explained. At discharge, patients should be told the expected recovery time, and the consequences of the operation on daily life.

 

 

Gynecol Obstet Fertil Senol. 2018 Mar 9. pii: S2468-7189(18)30051-5. doi: 10.1016/j.gofs.2018.02.019. [Epub ahead of print]

[Interest of hysterectomy with or without bilateral oophorectomy in the surgical treatment of endometriosis: CNGOF-HAS Endometriosis Guidelines].

Niro J¹, Panel P².

Abstract

OBJECTIVE:

In women with symptomatic endometriosis and no desire for pregnancy, hysterectomy with or without bilateral oophorectomy is often presented as a definitive solution to their symptoms. Despite this radical treatment, it should be known that nearly 15% of these patients will have persistent pain. Thus the objective of this review was to determine the interest of total hysterectomy with or without bilateral oophorectomy for the treatment of deep endometriosis.

METHOD:

The research was conducted from the US National Library of Medicine’s National Institutes of Health from the following keywords: endometriosis, hysterectomy, oophorectomy, ovariectomy, radical treatment. Only articles written in English have been selected.

RESULTS AND RECOMMENDATIONS:

Hysterectomy with or without bilateral oophorectomy, associated with endometriotic lesions exeresis could decrease the rate of recurrence and surgical reoperations compared to resection alone endometriosislesions (NP4). In women with no desire for pregnancy, the benefit-risk balance of a hysterectomy, with or without bilateral oophorectomy, may be discussed in order to reduce the risk of recurrence of endometriotic disease (Expert Agreement). Taking into account the multiple adverse effects of early menopause on expectancy and quality of life (NP2), ovarian preservation should be discussed with the patient in case of hysterectomy for deep endometriosis (Expert Agreement). The use of menopausal hormone therapy (THM) does not appear to increase the symptoms of endometriosis after surgical castration (NP3). THM is not contraindicated in postmenopausal women with endometriosis (grade C).

 

 

 

Gynecol Obstet Fertil Senol. 2018 Mar 9. pii: S2468-7189(18)30042-4. doi: 10.1016/j.gofs.2018.02.010.

[Endometriosis and fertility preservation: CNGOF-HAS Endometriosis Guidelines].

Decanter C¹, d’Argent EM², Boujenah J³, Poncelet C⁴, Chauffour C⁵, Collinet P⁶, Santulli P⁷.

 

Abstract

Fertility preservation (FP) techniques are progressing rapidly these past few years thanks to the oocyte vitrification. Indication of FP techniques is now extended to non-oncological situation that may induce risk of premature ovarian failure. Ovarian endometriosis can lead to premature ovarian failure and further infertility due to the high risk of ovarian cysts recurrence and surgery. To date, there is no cohort study regarding FP and endometriosis as well as no recommendation. Our purpose is to review the arguments in favor of FP in this specific area and to elaborate strategies according to each clinical form.

 

 

 

Gynecol Obstet Fertil Senol. 2018 Mar 10.

Endometriosis medical treatment: Hormonal treatment for the management of pain and endometriotic lesions recurrence. CNGOF-HAS Endometriosis Guidelines.

 

Geoffron S¹, Cohen J², Sauvan M³, Legendre G⁴, Wattier JM⁵, Daraï E², Fernandez H⁶, Chabbert-Buffet N⁷.

 

Abstract

The available literature, from 2006 to 2017, on hormonal treatment has been analysed as a contribution to the HAS-CNGOF task force for the treatment of endometriosis. Available data are heterogeneous and the general level of evidence is moderate. Hormonal treatment is usually offered as the primary option to women suffering from endometriosis. It cannot be used in women willing to conceive. In women who have not been operated, the first line of hormonal treatment includes combined oral contraceptives (COC) and the levonorgestrel-releasing intra uterine system (52mg LNG-IUS). As a second line, desogestrel progestin only pills, etonogestrel implants, GnRH analogs (GnRHa) with add back therapy and dienogest can be offered. Add back therapy should include estrogens to prevent bone loss and improve quality of life, it can be introduced before the third month of treatment to prevent side effects. The literature does not support preoperative hormonal treatment for the sole purpose of reducing complications or recurrence, or facilitating surgical procedures. After surgical treatment, hormonal treatment is recommended to prevent pain recurrence and improve quality of life. COCs or LNG IUS are recommended as a first line. To prevent recurrence of endometriomas COC is advised and maintained as long as tolerance is good in the absence of pregnancy plans. In case of dysmenorrhea, postoperative COC should be used in a continuous scheme. GnRHa are not recommended in the sole purpose of reducing endometrioma recurrence risk.

 

 

Gynecol Obstet Fertil Senol. 2018 Mar 9. pii: S2468-7189(18)30041-2. doi: 10.1016/j.gofs.2018.02.009. [Epub ahead of print]

New medical treatments for painful endometriosis: CNGOF-HAS EndometriosisGuidelines.

Legendre G¹, Delbos L², Hudon E², Chabbert-Buffet N³, Geoffron S³, Sauvan M⁴, Fernandez H⁴, Bouet PE², Descamps P².

Abstract

OBJECTIVE:

The objective of this work is to evaluate the place of new treatments in the management of endometriosis outside the context of infertility.

METHODS:

A review of the literature was conducted by consulting Medline data until July 2017.

RESULTS:

Dienogest is effective compared to placebo in short term (NP2) and long term (NP4) for the treatment of painful endometriosis. In comparison with GnRH agonists, dienogest is also effective in terms of decreased pain and improved quality of life in non-operated patients (NP2) as well as for recurrence of lesions and symptomatology postoperatively (NP2). Data on GnRH antagonists, selective progesterone receptor modulators as well as selective inhibitors (anti-TNF-α, matrix metalloprotease inhibitors, angiogenesis growth factor inhibitors) are insufficient to provide evidence of interest in clinical practice for the management of painful endometriosis (NP3).

CONCLUSION:

Dienogest is recommended as second-line therapy for the management of painful endometriosis (Grade B). Because of lack of evidence, aromatase inhibitors, elagolix, SERM, SPRM and anti-TNF-α are not recommended for the management of painful endometriosis (Grade C).

 

 

 

Gynecol Obstet Fertil Senol. 2018 Mar 9. pii: S2468-7189(18)30054-0. doi: 10.1016/j.gofs.2018.02.022.

Specific clinical signs suggestive of endometriosis (excluding adenomyosis) and questionnaires of symptoms, pain and quality of life: CNGOF-HAS EndometriosisGuidelines.

 

Huchon C¹, Aubry G², Ploteau S³, Fauconnier A⁴.

 

Abstract

In case of consultation for chronic pelvic pain or suspicion of endometriosis, it is recommended to evaluate the pain (intensity, resonance) and to search out the evocative and localizing symptoms of endometriosis (Grade B). The main symptoms suggestive of endometriosis are: severe dysmenorrhea (NP2), deep dyspareunia (NP2), painful defecation during menstruation (NP2), urinary tract symptoms during menstruation (NP2) and infertility (NP2). In patients with chronic pelvic pain, it is recommended to search deep infiltrating endometriosis in patients with painful defecation during menstruation or severe deep dyspareunia (Grade B). It is recommended to search symptoms suggestive of sensitization in painful patients with endometriosis (Grade B). When suggestive symptoms of endometriosis are present, a directed gynecological examination is recommended, where possible, including examination of the posterior vaginal cul-de-sac (Grade C). In assessing pain intensity or evaluating analgesic effectiveness of a treatment, it is recommended to use a scale to measure the intensity of pain (Grade A). In the management of symptomatic endometriosis, it is recommended to evaluate the quality of life (Grade C).

 

 

 

Gynecol Obstet Fertil Senol. 2018 Mar 9. pii: S2468-7189(18)30056-4. doi: 10.1016/j.gofs.2018.02.024. [Epub ahead of print]

Diagnosis accuracy of endoscopy (laparoscopy, hysteroscopy, fertiloscopy, cystoscopy, colonoscopy) in case of endometriosis: CNGOF-HAS Endometriosis Guidelines.

Tardieu A¹, Sire F¹, Gauthier T².

Abstract

OBJECTIVE:

To provide clinical practice guidelines from the French college of obstetrics and gynecology (CNGOF) with the Haute Autorité de santé (HAS), based on the best evidence available, concerning the diagnosis accuracy of endoscopy (laparoscopy, hysteroscopy, fertiloscopy, cystoscopy, colonoscopy) in case of endometriosis.

MATERIAL AND METHODS:

English and French review of literature about the diagnosis accuracy of endoscopy in case of endometriosis.

RESULTS AND CONCLUSION:

Laparoscopy is useful in case of suspected endometriosis in patients with symptoms or infertility when appropriate preoperative assessment is negative (grade C). Biopsies during diagnosis laparoscopy are recommended in case of typical or atypical lesions to confirm endometriosis (grade B). It is not recommended to perform fertiloscopy in case of suspected endometriosis (grade C). Hysteroscopy could be performed in case of suspected endometriosis and infertility to eliminate endometrial polyp or septate uterus (grade C). Colonoscopy is not recommended in case of suspected deep posterior endometriosis (grade C).

Copyright © 2018 Elsevier Masson SAS. All rights reserved.

 

 

 

Am J Nucl Med Mol Imaging. 2018 Feb 5;8(1):15-31. eCollection 2018.

Preparation and evaluation of a 68Ga-labeled RGD-containing octapeptide for noninvasive imaging of angiogenesis: biodistribution in non-human primate.

Velikyan I¹, Lindhe Ö².

 

Abstract

Monitoring general disease marker such as angiogenesis may contribute to the development of personalized medicine and improve therapy outcome. Readily availability of positron emitter based imaging agents providing quantification would expand clinical positron emission tomography (PET) applications. Generator produced ⁶⁸Ga provides PET images of high resolution and the half-life time frame is compatible with the pharmacokinetics of small peptides comprising arginine-glycine-aspartic acid (RGD) sequence specific to α_vβ₃ integrin receptors. The main objective of this study was to develop a method for ⁶⁸Ga-labeling of RGD containing bicyclic octapeptide ([⁶⁸Ga]Ga-DOTA-RGD) with high specific radioactivity and preclinically assess its imaging potential. DOTA-RGD was labeled using generator eluate preconcentration technique and microwave heating. The binding and organ distribution properties of [⁶⁸Ga]Ga-DOTA-RGD were tested in vitro by autoradiography of frozen tumor sections, and in vivo in mice carrying a Lewis Lung carcinoma graft (LL2), and in non-human primate (NHP). Another peptide with aspartic acid-glycine-phenylalanine sequence was used as a negative control. The full ⁶⁸Ga radioactivity eluted from two generators was quantitatively incorporated into 3-8 nanomoles of the peptide conjugates. The target binding specificity was confirmed by blocking experiments. The specific uptake in the LL2 mice model was observed in vivo and confirmed in the corresponding ex vivo biodistribution experiments. Increased accumulation of the radioactivity was detected in the wall of the uterus of the female NHP probably indicating neovascularization. [⁶⁸Ga]Ga-DOTA-RGD demonstrated potential for the imaging of angiogenesis.

 

 

J Am Coll Nutr. 2018 Mar 13:1-6. doi: 10.1080/07315724.2018.1431160. [Epub ahead of print]

The Relationship Between Female Reproductive Functions and Vitamin D.

Arslan S¹, Akdevelioğlu Y¹.

 

Abstract

Nonclassical target organs recently defined for vitamin D, a major regulator of calcium phosphorus homeostasis and bone health, include reproductive ones. This compilation study focuses on the potential effects of vitamin D on female reproductive functions. Vitamin D receptor enzymes that metabolize vitamin D are expressed in both central and peripheral reproductive organs. Most studies suggest that vitamin D may be directly or indirectly related to gonadal functions. Vitamin D’s effects on reproductive functions may be indirectly related to diseases such as polycystic ovary syndrome (PCOS), uterine leiomyomas, and endometriosis. In case of vitamin D deficiency during infertility treatment, vitamin D supplementation can be recommended especially for women who have PCOS, insulin resistance, or low anti-Mullerian hormone levels. Supplementation, however, should take into account possible toxic effects of high-dose vitamin D. To be able to recommend measuring vitamin D as a routine screening test and to better understand the effects of vitamin D and its supplementation on female reproductive functions, larger randomized controlled prospective studies are needed.

 

 

 

Adv Clin Exp Med. 2018 Mar 13. doi: 10.17219/acem/68845. [Epub ahead of print]

Telocytes in the female reproductive system: An overview of up-to-date knowledge.

Janas P¹, Kucybała I¹, Radoń-Pokracka M¹, Huras H¹.

 

Abstract

Telocytes are emerging cell population localized in the stroma of numerous organs, characterized by a distinctive morphology – small cell body with very long, slender prolongations, termed telopodes. Those cells can be found in the whole female reproductive system: in the vagina, uterus, oviducts and ovaries, mammary glands and also in the placenta. In our review, we aim at complete and transparent revision of the current knowledge of telocytes’ localization and function, enriched by the analysis of the possible future direction of development of their clinical applications. The function of telocytes in the reproductive system has not been fully elucidated yet; however, many researchers point at their role in the regulation of local microenvironment, myogenic contractile mechanism, bioelectrical signaling, immunomodulation and regulation of blood flow. Additionally, previous research suggests that telocytes might act as sex hormone level sensors and are connected with pregnancy maintenance. As the morphology and number of those cells change under pathological conditions, such as pre-eclampsia, endometriosis and ovarian failure, there is a chance that they may contribute to therapy of abovementioned conditions. The impact of telocytes on stem cells and angiogenesis has been proven in many organs, and may be useful in regenerative medicine of the female reproductive system. A recently found connection between the proliferation rate of breast cancer cells and stromal cells like telocytes might be a step forward to the management of mammary gland neoplasms.

 

 

 

Zhonghua Fu Chan Ke Za Zhi. 2018 Feb 25;53(2):92-98. doi: 10.3760/cma.j.issn.0529-567X.2018.02.005.

Analysis of characteristics and influence factors of diagnostic delay of endometriosis.

 

Han XT¹, Guo HY, Kong DL, Han JS, Zhang LF.

 

Abstract

in English, Chinese

Objective: To access the influence factors of diagnostic delay of endometriosis. Methods: We designed a questionnaire of diagnostic delay of endometriosis. From February 2014 to February 2016, 400 patients who had dysmenorrhea and diagnosed with endometriosis by surgery in Peking University Third Hospital were surveyed retrospectively. Time and risk factors of diagnostic delay were analyzed. Results: The diagnostic delay of 400 patients was 13.0 years (0.2-43.0 years), 78.5%(314/400) patients thought pain was a normal phenomenon and didn’t see the doctor. Patients who suffered dysmenorrhea at menarche experienced longer diagnostic delay than those who had dysmenorrhea after menarche (18.0 vs 4.5 years; Z=191.800, P<0.01) . Patients who suffered aggravating dysmenorrhea experienced shorter delay time than those who suffered stable or relieving dysmenorrhea (11.0 vs 12.5 vs 18.0 years; Z=8.270, P<0.05) , with the difference statistically significant, single factor analysis shows. Severe dysmenorrhea, deep infiltration endometriosis (DIE) , family history of dysmenorrhea or endometriosis, previous surgical history of endometriosis, high stage, with infertility, adenomyoma or other symptoms, could help to shorten diagnostic delay with no significant difference (P>0.05) . By multiple logistic regression analysis, the results shown that whether have dysmenorrhea at menarche and clinical diagnosis time were the independent factors affecting delayed diagnosis (P<0.01) . Conclusions: Diagnostic delay of endometriosis is common and the mean delay time is 13.0 years mainly due to the unawareness of dysmenorrhea. Dysmenorrhea at menarche, clinical diagnosis time and dysmenorrhea intensity are the factors affecting time of diagnostic delay.

 

 

 

Gynecol Obstet Fertil Senol. 2018 Mar 10. pii: S2468-7189(18)30035-7. doi: 10.1016/j.gofs.2018.02.003.

 

Surgical management of deep endometriosis with colorectal involvement: CNGOF-HAS Endometriosis Guidelines.

 

Ballester M¹, Roman H².

 

Abstract

Deep endometriosis with colorectal involvement is considered one of the most severe forms of the disease due to its impact on patients’ quality of life and fertility but also by the difficulties encountered by the clinicians when proposing a therapeutic strategy. Although the literature is very rich, evidence based medicine remains poor explaining the great heterogeneity concerning the management of such patients. Surgery therefore remains a therapeutic option. It improves the intensity of gynecological, digestive and general symptoms and the quality of life. Concerning the surgical approach, it appears that laparoscopy should be the first option; the laparoscopic robot-assisted route can also be proposed. The techniques of rectal shaving, discoid resection and segmental resection are the three techniques used for surgical excision of colorectal endometriosis. The parameters taken into account for the use of either technique are: the surgeon’s experience, the depth of infiltration of the lesion within the rectosigmoid wall, the lesion size and circumference, multifocality and the distance of the lesion from the anal margin. In the case of deep endometriosis with colorectal involvement, performing an incomplete surgery increases the rate of pain recurrence and decreases postoperative fertility. In case of surgery for colorectal endometriosis, pregnancy rates are similar to those obtained after ART in non-operated patients. Existing data are insufficient to formally recommend first line surgery or ART in infertile patients with colorectal endometriosis. The surgery for colorectal endometriosis exposes to a risk of postoperative complications and recurrence of which the patients should be informed preoperatively.

 

 

 

Toxicol Lett. 2018 Mar 10. pii: S0378-4274(18)30096-1. doi: 10.1016/j.toxlet.2018.03.009. [Epub ahead of print]

Polychlorinated biphenyl 104 promotes migration of endometrial stromal cells in endometriosis.

Hu T¹, Yao M¹, Fu X¹, Chen C¹, Wu R².

 

Abstract

Polychlorinated biphenyls (PCBs), as part of environmental contaminants, have been proved to be related to endometriosis. This study is to investigate the effect of PCB 104 on cell migration, invasion and resultant gene expression in endometrial stromal cells (ESCs). Fifty-three specimens of eutopic endometrial tissues were collected from twenty-four women with endometriosis (EU-EMS) and twenty-nine women without endometriosis (EU-NON). Both EU-EMS and EU-NON were divided into the PCB 104 exposure group and the control group according to whether they were exposed to PCB 104. Primary cultured ESCs were exposed to PCB 104 at the micro molar doses (2 × 10^-3, 0.2 and 1 μmol/L) and concentrations of 2, 5 and 10 μmol/L in six-well plates. Cell mobility and proliferation assay were used to evaluate the effects of PCB 104 on the migration, invasion and proliferation of ESCs, and the effect of PCB 104 on actin cytoskeleton was also examined by immunofluorescence. Subsequently, the mRNA levels of related genes including matrix metalloproteinase (MMP) -2, -3, -9, -10, E-cadherin, Snail, Slug and tissue inhibitor of metalloproteinase (TIMP) -2 in ESCs were examined by using real-time PCR, as well as protein levels of MMP-3 and MMP-10 were detected by enzyme-linked immunosorbent assay (ELISA). We explored the role of epidermal growth factor receptor (EGFR) in the expression of MMP-3 and MMP-10 induced by PCB 104. Exposure to PCB 104 significantly increased the migration and invasion of ESCs. The mRNA and protein levels of MMP-3 and MMP-10 in ESCs treated with PCB 104 were higher than that in the control, with a dose- and time-dependent manner in mRNA level, while the expression of MMP-2, MMP-9, TIMP-2, E-cadherin, Snail and Slug did not change significantly. Taken together, PCB 104 promotes migration and invasion of ESCs by inducing the expression of MMP-3 and MMP-10, which may involved the EGFR signalling pathway.

 

 

 

Stem Cells Int. 2018 Jan 28;2018:7318513. doi: 10.1155/2018/7318513. eCollection 2018.

Mesenchymal Stromal Cells Support Endometriotic Stromal Cells In Vitro.

Abomaray F^1,2, Gidlöf S^1,3,4, Bezubik B⁵, Engman M⁶, Götherström C^1,2.

 

Abstract

Endometriosis is an inflammatory disease marked by ectopic growth of endometrial cells. Mesenchymal stromal cells (MSC) have immunosuppressive properties that have been suggested as a treatment for inflammatory diseases. Therefore, the aim herein was to examine effects of allogeneic MSC on endometriosis-derived cells in vitro as a potential therapy for endometriosis. MSC from allogeneic adipose tissue (Ad-MSC) and stromal cells from endometrium (ESC_endo) and endometriotic ovarian cysts (ESC_cyst) from women with endometriosis were isolated. The effects of Ad-MSC on ESC_endo and ESC_cyst were investigated using in vitro proliferation, apoptosis, adhesion, tube formation, migration, and invasion assays. Ad-MSC significantly increased proliferation of ESC compared to untreated controls. Moreover, Ad-MSC significantly decreased apoptosis and increased survival of ESC. Ad-MSC significantly increased adhesion of ESC_endo and not ESC_cyst on fibronectin. Conditioned medium from cocultures of Ad-MSC and ESC significantly increased tube formation of human umbilical vein endothelial cells on matrigel. Ad-MSC may significantly increase migration of ESC_cyst and did not increase invasion of both cell types. The data suggest that allogeneic Ad-MSC should not be considered as a potential therapy for endometriosis, because they may support the pathology by maintaining and increasing growth of ectopic endometrial tissue.

 

 

 

J Obstet Gynaecol. 2018 Mar 14:1-5. doi: 10.1080/01443615.2017.1410533. [Epub ahead of print]

A comparison of two different oral contraceptives in patients with severe primary dysmenorrhoea.

Uysal G¹, Akkaya H², Cagli F³, Tutus S⁴, Tayyar AT⁵.

 

Abstract

Pain relief of two different oral contraceptive pills (OCPs) in severe primary dysmenorrhoea (PD) was compared. Sixty-six nulliparous patients with severe PD requiring contraception were evaluated. Group 1 comprised 33 healthy controls. Patients with severe PD were divided into two groups. Patients in Group 2 were administered oestradiol valerate/dienogest and patients in Group 3 were administered ethinylestradiol/drospirenone. Doppler indices of both uterine arteries (left and right) including systolic/diastolicrates (S/D), pulsatility index (PI) and resistance index (RI) were measured, and a visual analogue scale (VAS) was applied to patients before treatment. VAS scores and Doppler indices were repeated after 3 months of OCP treatment and the changes in values were compared. The demographic and clinical characteristics of the patients were similar. The mean value of RI was significantly lower after therapy in Groups 2 and 3 in the right and left uterine arteries (p = .001 and p = .039, respectively). The clinical trial number was NCT03124524. Impact Statement What is already known on this subject: OCPs are the most appropriate treatment option for PD. There is no clear data about OCP containing dienogest for treatment in PD. Dienogest has been reported to be highly effective in the treatment of endometriosis and is also recommended as first-line therapy for pelvic pain-associated endometriosis. What the results of this study add: In this study, although there was no superiority in pain relief between the treatment groups, lower VAS scores and lower RI values of uterine arteries were seen after treatment. Both OCPs relieve pain in severe PD. There was no serious adverse effect in the patients. What the implications are of these findings for clinical practice and/or further research: Estradiol valerate/dienogest, which is a routinely prescribed drug for heavy menstrual bleeding in women who desire oral contraception, is as effective as ethinylestradiol/drospirenone in pain relief.

 

 

 

Reprod Sci. 2018 Jan 1:1933719118764255. doi: 10.1177/1933719118764255. [Epub ahead of print]

Enhanced UGT1A1 Gene and Protein Expression in Endometriotic Lesions.

Piccinato CA^1,2, Neme RM^1,3, Torres N¹, da Silva Victor E¹, Brudniewski HF^1,3, Rosa E Silva JC², Ferriani RA².

 

Abstract

The cellular function in endometriosis lesions depends on a highly estrogenic milieu. Lately, it is becoming evident that, besides the circulating levels of estrogens, the balance of synthesis versus inactivation (metabolism) of estrogens by intralesion steroid-metabolizing enzymes also determines the local net estrogen availability. In order to extend the knowledge of the role of estrogen-metabolizing enzymes in endometriosis, we investigated the gene and protein expression of a key uridine diphospho-glucuronosyltransferase (UGT) for estrogen glucuronidation, UGT1A1, in eutopic endometrial samples obtained from nonaffected and endometriosis-affected women and also from endometriotic lesions. Although UGT1A1 messenger RNA (mRNA) expression was detected at similar frequencies in endometriotic lesions and in eutopic endometrial samples, the levels of mRNA expression were greater in deep-infiltrating endometriotic lesions and in non-deep-infiltrating lesions when compared with either control endometrium or eutopic endometrium from women with endometriosis. Overall, we observed that protein expression of UGT1A1 was significantly more frequent in samples from endometriotic lesions in comparison with endometria. In addition, expression of UGT1A1 protein was greater in deep-infiltrating than in non-deep-infiltrating endometriotic lesions. We suggest that the finding of increased expression of UGT1A1 in lesions versus endometria might be related to impairment of regulatory mechanisms, in response to a highly estrogenic milieu, and that this enzyme may be a new target for therapy.

 

 

 

Gynecol Obstet Fertil Senol. 2018 Mar 11. pii: S2468-7189(18)30055-2. doi: 10.1016/j.gofs.2018.02.023. [Epub ahead of print]

Diagnostic performance of MR imaging, coloscan and MRI/CT enterography for the diagnosis of pelvic endometriosis: CNGOF-HAS Endometriosis Guidelines.

 

Thomassin-Naggara I¹, Bendifallah S², Rousset P³, Bazot M⁴, Ballester M², Darai E⁵.

 

Abstract

Diagnostic performance of MR imaging for the diagnosis of pelvic endometriosis are good. Even if some differences of performances exists according the location considered, the risk of misdiagnosis is lower than 10% for trained teams (NP2). The performance of pelvic MR imaging and surgery are quite similar to diagnose endometrioma (sensitivity and specificity>90%). A negative pelvic MR imaging allows to exclude deep pelvic endometriosis with a performance similar to surgery but a positive MR imaging is less accurate than surgery because of a high number of false positives (23%). Pelvic MR imaging is more sensitive and less specific than ultrasonography for the diagnosis of uterosacral ligament, vagina or recto vaginal septum (NP2). Pelvic ultrasonography is more sensitive than pelvic MR imaging for the diagnosis of colorectal location (NP3). Pelvic MR imaging is a reproducible technique for the diagnosis of pelvic endometriosis (NP3). Regarding, quality criteria of pelvic MR imaging, no data are enough to recommend a specific MR unit, digestive preparation, or a specific moment during the menstrual cycle to realize the examination. Vaginal and/or rectal opacification are options. Most of studies are based a protocol including 3D T2W and 3DT1W sequences. Gadolinium injection is useful to characterize a complex adnexal mass. In clinical routine, slices crossing the kidneys are useful to evaluate the presence of pyelo calic distension. ColoCT is an accurate technique to diagnose pelvic digestive endometriosis (rectosigmoide and iléocaecal) (NP3).

 

 

 

Gynecol Obstet Fertil Senol. 2018 Mar 11. pii: S2468-7189(18)30049-7. doi: 10.1016/j.gofs.2018.02.017.

Definition, description, clinicopathological features, pathogenesis and natural history of endometriosis: CNGOF-HAS Endometriosis Guidelines.

Borghese B¹, Santulli P², Marcellin L³, Chapron C².

 

Abstract

Endometriosis and adenomyosis are histologically defined. The frequency of endometriosis cannot be precisely estimated in the general population. Endometriosis is considered a disease when it causes pain and/or infertility. Endometriosis is a heterogeneous disease with three well-recognized subtypes that are often associated with each other: superficial endometriosis(SUP), ovarian endometrioma (OMA), and deep infiltrating endometriosis (DIE). DIE is frequently multifocal and mainly affects the following structures: the uterosacral ligaments, the posterior vaginal cul-de-sac, the bladder, the ureters, and the digestive tract (rectum, recto-sigmoid junction, appendix). The role of menstrual reflux in the pathophysiology of endometriosis is major and explains the asymmetric distribution of lesions, which predominate in the posterior compartment of the pelvis and on the left (NP3). All factors favoring menstrual reflux increase the risk of endometriosis (early menarche, short cycles, AUB, etc.). Inflammation and biosteroid hormones synthesis are the main mechanisms favoring the implantation and the growth of the lesions. Pain associated with endometriosis can be explained by nociception, hyperalgia, and central sensitization, associated to varying degrees in a single patient. Typology of pain (dysmenorrhea, deep dyspareunia, digestive or urinary symptoms) is correlated with the location of the lesions. Infertility associated with endometriosis can be explained by several non-exclusive mechanisms: a pelvic factor (inflammation), disrupting natural fertilization; an ovarian factor, related to oocyte quality and/or quantity; a uterine factor disrupting implantation. The pelvic factor can be fixed by surgical excision of the lesions that improves the chance of natural conception (NP2). The uterine factor can be corrected by an ovulation-blocking treatment that improves the chances of getting pregnant by in vitro fertilization (NP2). The impact of endometrioma exeresis on the ovarian reserve (NP2) should be considered when a surgery is scheduled. Endometriosis is a multifactorial disease, resulting from combined action of genetic and environmental factors. The risk of developing endometriosis for a first-degree relative is five times higher than in the general population (NP2). Identification of genetic variants involved in the disease has no implication for clinical practice for the moment. The role of environmental factors, particularly endocrine disrupters, is plausible but not demonstrated. Literature review does not support the progression of endometriosis over time, either in terms of the volume or the number of the lesions (NP3). The risk of acute digestive occlusion or functional loss of a kidney in patients followed for endometriosis seems exceptional. These complications were revealing the disease in the majority of cases. IVF does not increase the intensity of pain associated with endometriosis (NP2). There is few data on the influence of pregnancy on the lesions, except the possibility of a decidualization of the lesions that may give them a suspicious aspect on imaging. The impact of endometriosis on pregnancy is debated. There is an epidemiological association between endometriosis and rare subtypes of ovarian cancer (endometrioid and clear cell carcinomas) (NP2). However, the relative risk is moderate (around 1.3) (NP2) and the causal relationship between endometriosis and ovarian cancer is not demonstrated so far. Considering the low incidence of endometriosis-associated ovarian cancer, there is no argument to propose a screening or a risk reducing strategy for the patients.

 

 

 

Gynecol Endocrinol. 2018 Mar 16:1-6. doi: 10.1080/09513590.2018.1451506. [Epub ahead of print]

Upregulation of S100A6 in patients with endometriosis and its role in ectopic endometrial stromal cells.

Peng Y¹, Lin J¹, Ma J², Lin K¹, Xu K¹, Lin J¹.

 

Abstract

S100 calcium-binding protein A6 (S100A6) is up-regulated in many malignancies and overexpression of S100A6 has been identified associated with proliferation, migration and invasion phenotype in several cancer cells. In the present study, we explored whether S100A6 plays a role in the development of endometriosis. Significantly higher levels of mRNA and protein expression of S100A6 were observed in ectopic endometrial tissues compared to eutopic and normal endometrial tissues. Silencing of S100A6 in ectopic endometrial stromal cells (ESCs) significantly inhibited cell viability, migration and invasion. Moreover, knockdown of S100A6 suppressed p38/MAPK activity in ectopic ESCs, which can be partially attenuated by CacyBP/SIP phosphorylation inhibitor. In conclusion, our results suggest that the abnormal expression of S100A6 may contribute to the pathogenesis of endometriosis and the S100A6/CacyBP/p38 signaling may provide as a promising treatment target.

 

 

 

Gynecol Obstet Fertil Senol. 2018 Mar 12. pii: S2468-7189(18)30058-8. doi: 10.1016/j.gofs.2018.02.026.

 

Performances and place of sonography in the diagnostic of endometriosis: CNGOF-HAS Endometriosis Guidelines.

Philip CA¹, Dubernard G².

 

Abstract

Endometriosis is difficult to diagnose clinically. Transvaginal sonography (TVS) is a procedure that is known to be operator-dependent, which mean that published evidences has to be balanced with the level of the sonographer that produced the data. The objective of this publication was to assess the performances of the sonography in the diagnosis of endometriosis in order to establish the French national recommendations. We searched the MEDLINE database for publication from January 2000 to September 2017 using keywords associated with endometriosis and sonography. Eighty-four trial and reviews published in English or French were included. Ovarian endometrioma can usually be diagnosed by a non-expert sonographer, especially when its aspect is typical. In case of an ovarian cyst with atypical presentation, it is recommended to control the sonography by a referent or to perform an MRI. In menopaused women, any ovarian cyst should be considered as a cancer until proven otherwise. In the diagnosis of posterior deep invasive endometriosis (DIE), TVS with sensitivity and specificity of 96 and 99% respectively, seems at least equivalent if not superior to MRI. However, these performances are related to expert sonographers. To reach sufficient efficiency in posterior DIE, the estimated learning curve for a sonographer is 44 cases. When posterior DIE is suspected, we recommend proposing a TVS “performed by an expert” or a MRI “at least interpreted by an expert”. In anterior DIE, TVS has a good specificity (100%), but its sensitivity is poor in the literature (64%). TVS is therefore not able to eliminate the diagnosis. However a renal ultrasound should be proposed each time a urinary endometriosis is confirmed, and should be considered whenever posterior DIE is diagnosed especially the lesion is superior to 3cm.

 

 

 

Gynecol Obstet Fertil Senol. 2018 Mar 12. pii: S2468-7189(18)30038-2. doi: 10.1016/j.gofs.2018.02.006.

 

Deeply infiltrating endometriosis and infertility: CNGOF-HAS Endometriosis Guidelines.

 

Mathieu d’Argent E¹, Cohen J², Chauffour C³, Pouly JL³, Boujenah J⁴, Poncelet C⁵, Decanter C⁶, Santulli P⁷.

 

Abstract

Deeply infiltrating endometriosis is a severe form of the disease, defined by endometriotic tissue peritoneal infiltration. The disease may involve the rectovaginal septum, uterosacral ligaments, digestive tract or bladder. Deeply infiltrating endometriosis is responsible for disabling pain and infertility. The purpose of these recommendations is to answer the following question: in case of deeply infiltrating endometriosis associated infertility, what is the best therapeutic strategy? First-line surgery and then in vitro fertilization (IVF) in case of persistent infertility or first-line IVF, without surgery? After exhaustive literature analysis, we suggest the following recommendations: studies focusing on spontaneous fertility of infertile patients with deeply infiltrating endometriosisfound spontaneous pregnancy rates about 10%. Treatment should be considered in infertile women with deeply infiltrating endometriosis when they wish to conceive. First-line IVF is a good option in case of no operated deeply infiltrating endometriosisassociated infertility. Pregnancy rates (spontaneous and following assisted reproductive techniques) after surgery (deep lesions without colorectal involvement) varie from 40 to 85%. After colorectal endometriosis resection, pregnancy rates vary from 47 to 59%. The studies comparing the pregnancy rates after IVF, whether or not preceded by surgery, are contradictory and do not allow, to date, to conclude on the interest of any surgical management of deep lesions before IVF. In case of alteration of ovarian reserve parameters (age, AMH, antral follicle count), there is no argument to recommend first-line surgery or IVF. The study of the literature does not identify any prognostic factors, allowing to chose between surgical management or IVF. The use of IVF in the indication “deep infiltrating endometriosis” allows satisfactory pregnancy rates without significant risk, regarding disease progression or oocyte retrieval procedure morbidity.

 

 

 

Best Pract Res Clin Obstet Gynaecol. 2018 Feb 8. pii: S1521-6934(18)30026-9. doi: 10.1016/j.bpobgyn.2018.01.008. [Epub ahead of print]

Psychosocial impact of endometriosis: From co-morbidity to intervention.

Aerts L¹, Grangier L¹, Streuli I¹, Dällenbach P¹, Marci R¹, Wenger JM¹, Pluchino N².

 

Abstract

Endometriosis-associated pelvic pain is a major health concern in women of childbearing age. Controlled studies have shown that endometriosis can adversely affect women and their partners’ general psychological well-being, relationship adjustment and overall quality of life. Furthermore, women with endometriosis report significantly more sexual dysfunctions compared to healthy women. Empirical studies indicate that specific psychosocial factors may modulate pain experience, pain-related distress and treatment outcome. Research on psychosexual interventions in endometriosis treatment is limited but shows to be effective in reducing endometriosis-related pain and associated psychosexual outcomes. An individualized, couple-centered, multimodal approach to care, integrating psychosexual and medical management for endometriosis, is thought to be optimal.

 

 

 

Best Pract Res Clin Obstet Gynaecol. 2018 Feb 16. pii: S1521-6934(18)30038-5. doi: 10.1016/j.bpobgyn.2018.01.020. [Epub ahead of print]

Surgical treatment of different types of endometriosis: Comparison of major society guidelines and preferred clinical algorithms.

Kho RM¹, Andres MP², Borrelli GM³, Neto JS⁴, Zanluchi A⁵, Abrão MS⁶.

 

Abstract

Treatment options for patients with different types of endometriosis – superficial, ovarian, or deep – vary depending on the clinical presentation. New findings in the recent years regarding the role of preoperative imaging, efficacy of medical therapy, and effect of surgery on ovarian reserve have changed the way we understand the disease and subsequently the way we treat our patients. Practicing clinicians frequently refer to published recommendations from major societies for treatment guidelines. This paper aims to present and compare the varying major society guidelines on the indications and best surgical treatment approach for the management of the different types of endometriosis. We also present our preferred surgical treatment algorithm given the evidence in the literature and our cumulative 30-year clinical experience in a large tertiary referral center.

 

 

 

J Minim Invasive Gynecol. 2018 Mar 12. pii: S1553-4650(18)30155-9. doi: 10.1016/j.jmig.2018.03.003. [Epub ahead of print]

Combined Transvaginal/Transabdominal Pelvic Ultrasonography Accurately Predicts the 3 Dimensions of Deep Infiltrating Bowel Endometriosis Measured after Surgery: a Prospective Study in a Specialized Center.: Diagnostic Value of TV/TA-US for Bowel DIE.

Di Giovanni A¹, Casarella L², Coppola M², Iuzzolino D², Rasile M², Malzoni M².

Abstract

STUDY OBJECTIVE:

To assess sensitivity and accuracy of combined transvaginal/transabdominal ultrasonography for evaluation of deep infiltrating bowel endometriosis nodules measured after surgery.

DESIGN:

A prospective study (Canadian Task Force classification II.1).

SETTING:

A Center for Advanced Endoscopic Gynecologic Surgery from January 2014 to December 2016.

PATIENTS:

All women undergoing laparoscopic surgery and scheduled for segmental resection for clinically suspected bowel endometriosis.

INTERVENTIONS:

In all women clinically suspected for bowel endometriosis, an ultrasound scan was performed before surgery to detect and measure the 3 diameters of bowel endometriotic lesions. These diameters were compared with those obtained by direct measurement on the fresh specimen. Sensitivity and specificity values of ultrasound evaluation were calculated, with 95% confidence intervals (CIs).

MEASUREMENTS AND MAIN RESULTS:

The sensitivity and specificity of transvaginal/transabdominal ultrasound, in the 328 patients of this study were 100% when rectal endometriotic lesions were investigated. The specificity was 100% while the sensitivity decreased to 91.4% when sigmoid lesions were investigated. Bowel muscularis infiltration was histologically confirmed in all cases (284/284; 100%) where endometriotic lesions were sonographically detected. All missed sigmoid lesions (12/296) were at a distance of >25 cm from the anal verge. Mean diameters of endometriotic nodules calculated by ultrasound evaluation and by direct measurement on fresh specimen were 43.19×19.87×10.79 mm and 42.76×19.64×10.62 mm respectively, without statistically significant differences between methods used.

CONCLUSION:

In conclusion, we believe that ultrasonography can be considered an accurate diagnostic technique for the evaluation of deep infiltrating bowel endometriosis when performed by a dedicated experienced sonographer in the setting of a specialized center .

Copyright © 2018. Published by Elsevier Inc.

 

 

 

J Turk Ger Gynecol Assoc. 2018 Mar 16. doi: 10.4274/jtgga.2017.0146. [Epub ahead of print]

Does the presence of endometriosis cause a challenge for transvaginal oocyte retrieval procedure? A comparison between patients with endometriosis and without endometriosis.

Kasapoğlu I¹, Türk P¹, Dayan A¹, Uncu G¹.

Abstract

OBJECTIVE:

The aim of the study was to compare patients with endometriosis to those without endometriosis regarding performance rates, difficulties and complications associated with transvaginal oocyte retrieval (TVOR) procedures.

MATERIAL AND METHODS:

A prospective cohort study was conducted at the IVF Unit of the Division of Reproductive Endocrinology and Infertility Department of an University Hospital. Fifty-eight patients with endometriosis and 61 patients without endometriosis underwent a TVOR procedure consecutively. Primary outcome measures were; number of needle entries per patient and performance rating defined as the number of total oocytes retrieved per vaginal needle entry. The requirement for manual compression of the abdominal wall (assistance) to reach the ovaries, procedure-related pain and procedural complications were also evaluated.

RESULTS:

The median number of needle entries through the vaginal wall per patient was comparable between the two groups (p=0.45). Performance rates were higher in the control group (p=0.001). Performance rates and total number of the needle entries through the vaginal wall were not significantly correlated with OMA diameter (r=0.28; p=0.68; r=0.275, p=0.068, respectively) in the endometriosis group. BMI scores were found to be correlated with the number of the needle entries and higher BMI scores were associated with higher numbers of vaginal wall punctures (p<0.001). The requirement for manual compression of the abdominal wall was significantly higher in the control group (57.4% vs 27.6%, p=0.001). A similar proportion of women needed analgesic medications after the TVOR procedure in both groups (10.3% vs 16.4%, p=0.33). Hospital readmissions for any complaint were also comparable between two groups (p=0.22). All of three women who were treated for pelvic infection were in the endometriosis group.

CONCLUSION:

Endometriosis seems to cause a challenge for TVOR that may have reflection on individual surgeon’s performance rates for the procedure, independently from the diameter of a pre-existing OMA or ovarian adhesions. Obesity is another factor that may present a challenge for the procedure.

 

 

 

Cureus. 2018 Jan 13;10(1):e2063. doi: 10.7759/cureus.2063.

Skin Endometriosis at the Caesarean Section Scar: A Case Report and Review of the Literature.

Alnafisah F¹, Dawa SK², Alalfy S¹.

 

Abstract

Cutaneous endometriosis is one of the rare gynecological conditions. Endometriosis is defined as the presence of endometrial glands and stroma outside the endometrial cavity. It commonly occurs in pelvic sites, such as the ovaries, cul-de-sac, bowel, or pelvic peritoneum. Endometriosis at the incisional scar is difficult to diagnose because of nonspecific symptoms. Usually, patients complain of pain at the site of the incision during menstruation. The main causes in most of the reported cases are obstetrical and gynecological surgeries. Endometrial tissues may be directly implanted in the scar during operation and, under hormonal stimulation, proliferate and form scar endometriosis. Diagnosis is usually made following histopathology. A wide excision is recommended to prevent recurrence. We report a case of a 33-year-old woman presenting with a brownish mass on the lateral aspect of the Pfannenstiel incision from a previous cesarean section scar. The symptoms appeared two years after her operation. The patient had cyclical pain and brownish discharge from the lesion during menstruation. Excision of the skin lesion with underlying subcutaneous tissue showed multiple, minute, firm hemorrhagic foci. Histopathology was performed and revealed a benign endometrial gland and stroma in the tissues, confirming the diagnosis of scar endometriosis. Cutaneous endometriosis is an uncommon gynecological condition and difficult to diagnose because of the nonspecific symptoms. Usually, it is confused with other dermatological and surgical diseases and delays the diagnosis and management. Surgical scar endometriosis following obstetric and gynecological procedures is more frequent recently due to an increase in the number of caesarian sections worldwide. Health care providers should suspect cutaneous endometriosis in any women with pain and a lump in the incisional scar after pelvic surgery.

 

 

 

Mutat Res. 2018 Mar 9;809:1-5. doi: 10.1016/j.mrfmmm.2018.03.001. [Epub ahead of print]

The presence of KRAS, PPP2R1A and ARID1A mutations in 101 Chinese samples with ovarian endometriosis.

Zou Y¹, Zhou JY², Guo JB², Wang LQ², Luo Y¹, Zhang ZY¹, Liu FY¹, Tan J³, Wang F¹, Huang OP⁴.

 

Abstract

Endometriosis is a potential premalignant disorder. The underlying molecular aberrations, however, are not fully understood. A recent exome sequencing study found that 25% (10/39) of deep infiltrating endometriosis harbored cancer driver gene mutations. However, it is unclear whether these mutations also exist in ovarian endometriosis. Here, a total of 101 ovarian endometriosissamples were analyzed for the presence of these gene mutations, including KRAS, PPP2R1A, PIK3CA and ARID1A. In addition, 6 other cancer-associated genes (BRAF, NRAS, HRAS, ERK1, ERK2 and PTEN) were also analyzed. In total, four somatic mutations were identified in three out of 101 ovarian endometriotic lesions (4%, 4/101), including a KRAS p.G12V, a PPP2R1A p.S256F and two ARID1A nonsense mutations (p.Q403* and p.G1926*); while no mutations were identified in the remaining 7 genes (BRAF, NRAS, HRAS, ERK1, ERK2, PTEN and PIK3CA). Note that the KRAS G12V and ARID1A Q403* mutations co-occurred in a 36-year-old sample who had a high serum CA125 (308.4 U/mL) and a late menarche age (18-year-old). Additionally, no mutations in any of the 10 genes were identified in either the healthy eutopic endometrial tissues from 85 control individuals without endometriosis, or in 62 healthy ovarian tissues from ovarian cysts samples (without endometriosis). Our study revealed, for the first time, the presence of classical cancer driver gene mutations in ovarian endometriosis. Furthermore, the co-occurrence of KRAS and ARID1A mutations was identified in a single individual for the first time. The observations of cancer driver gene mutations in our ovarian endometriosis samples, together with several prior observations, further support the notion that endometriosis is a premalignant disorder.

 

 

 

Gynecol Obstet Fertil Senol. 2018 Mar 13. pii: S2468-7189(18)30044-8. doi: 10.1016/j.gofs.2018.02.012. [Epub ahead of print]

[Epidemiology and diagnosis strategy: CNGOF-HAS Endometriosis Guidelines].

Fauconnier A¹, Borghese B², Huchon C³, Thomassin-Naggara I⁴, Philip CA⁵, Gauthier T⁶, Bourdel N⁷, Denouel A⁸, Torre A⁹, Collinet P¹⁰, Canis M⁷, Fritel X¹¹.

Abstract

Based on the best evidence available, we have provided guidelines for clinical practice to target the nature of endometriosis as a disease, the consequences of its natural history on management, and the clinical and imaging evaluation of the disease according to the level of care (primary care, specialized or referral). The frequency of endometriosis is unknown in the general population; endometriosis requires management when it causes symptoms (pain, infertility) or when it affect the function of an organ. In the absence of symptom, there is no need for follow-up or screening of the disease. Endometriosis may be responsible for various pain symptoms such as severe dysmenorrhea, deep dyspareunia, painful bowel movements or low urinary tract signs increasing with menstruation, or infertility. A careful evaluation of the symptoms and their impact on the quality of life should be made. The first-line examinations for the diagnosis of endometriosis are: digital examination and pelvic ultrasound. The second-line examinations are: the pelvic exam by an expert clinician, the pelvic MRI and/or the transvaginal ultrasound by an expert. MRI and ultrasound carrying different and complementary information. Other examinations may be considered as part of the pre-therapeutic assessment of the disease in case of specialized care. Diagnostic laparoscopy may be suggested in case of clinical suspicion of endometriosis whereas preoperative examinations have not proved the disease, it must be part of a management plan of endometriosis-related pain or infertility. During management, it is recommended to give comprehensive information on the different therapeutic alternatives, the benefits and risks expected from each treatment, the risk of recurrence, fertility, especially before surgery. The information must be personalized and take into account the expectations and preferences of the patient, and accompanied by an information notice given to the patient.

 

 

 

Best Pract Res Clin Obstet Gynaecol. 2018 Feb 19. pii: S1521-6934(18)30041-5. doi: 10.1016/j.bpobgyn.2018.01.023. [Epub ahead of print]

A focus on the distinctions and current evidence of endometriosis in adolescents.

de Sanctis V¹, Matalliotakis M², Soliman AT³, Elsefdy H⁴, Di Maio S⁵, Fiscina B⁶.

 

Abstract

Endometriosis (EM) occurring in adolescents presents distinct clinical and histologic characteristics compared to the disease in women. Because the symptoms of EM are nonspecific, often overlapping with those experienced in a range of gynecological and gastrointestinal conditions, the process of reaching a diagnosis of EM is often delayed. The diagnosis of EM is suspected depending on the history and the symptoms and signs, is corroborated by physical examination and imaging techniques, and is finally proved by histological examination of specimens collected during laparoscopy. Currently, there is insufficient evidence to make strong recommendations for management in adolescents who may have EM. This short report reviews some peculiarities of EM in adolescents and provides an update of recent knowledge of the diagnosis and treatment of EM. We hope that the present contribution may help to bring more attention to the clinical diagnosis of EM and consequently aid in decreasing diagnostic delay.

 

 

 

Gynecol Obstet Fertil Senol. 2018 Mar 14. pii: S2468-7189(18)30059-X. doi: 10.1016/j.gofs.2018.02.027. [Epub ahead of print]

[Management of endometriosis: CNGOF-HAS practice guidelines (short version)].

Collinet P¹, Fritel X², Revel-Delhom C³, Ballester M⁴, Bolze PA⁵, Borghese B⁶, Bornsztein N⁷, Boujenah J⁸, Bourdel N⁹, Brillac T¹⁰, Chabbert-Buffet N¹¹, Chauffour C¹², Clary N¹³, Cohen J⁴, Decanter C¹⁴, Denouël A¹⁵, Dubernard G¹⁶, Fauconnier A¹⁷, Fernandez H¹⁸, Gauthier T¹⁹, Golfier F²⁰, Huchon C²¹, Legendre G²², Loriau J²³, Mathieu-d’Argent E²⁴, Merlot B²⁵, Niro J²⁶, Panel P²⁶, Paparel P²⁷, Philip CA¹⁶, Ploteau S²⁸, Poncelet C²⁹, Rabischong B¹², Roman H³⁰, Rubod C³¹, Santulli P⁶, Sauvan M³², Thomassin-Naggara I³³, Torre A³⁴, Wattier JM³⁵, Yazbeck C³⁶, Canis M⁹.

 

Abstract

First-line investigations to diagnose endometriosis are clinical examination and pelvic ultrasound. Second-line investigations include pelvic examination performed by a referent clinician, transvaginal ultrasound performed by a referent, and pelvic MRI. It is recommended to treat endometriosis when it is symptomatic. First-line hormonal treatments recommended for the management of painful endometriosis are combined hormonal contraceptives or levonorgestrel 52mg IUD. There is no evidence to recommend systematic preoperative hormonal therapy for the unique purpose of preventing the risk of surgical complications or facilitating surgery. After endometriosis surgery, combined hormonal contraceptives or levonorgestrel SIU 52mg are recommended as first-line therapy in the absence of desire of pregnancy. In case of initial treatment failure, recurrence, or multiple organ involvement by endometriosis, medico-surgical and multidisciplinary discussion is recommended. The laparoscopic approach is recommended for the surgical treatment of endometriosis. HRT may be offered in postmenopausal women operated for endometriosis. In case of infertility related to endometriosis, it is not recommended to prescribe anti-gonadotropic hormone therapy to increase the rate of spontaneous pregnancy, including postoperatively. The possibilities of fertility preservation should be discussed with the patient in case of surgery for ovarian endometrioma.

 

 

 

BMJ Open. 2018 Mar 17;8(3):e018959. doi: 10.1136/bmjopen-2017-018959.

Nineteen and Up study (19Up): understanding pathways to mental health disorders in young Australian twins.

Couvy-Duchesne B^#1,2, O’Callaghan V^#1, Parker R², Mills N^1,2,3, Kirk KM², Scott J^4,5, Vinkhuyzen A^1,6, Hermens DF⁴, Lind PA², Davenport TA⁴, Burns JM⁷, Connell M⁸, Zietsch BP^2,9, Scott J⁸, Wright MJ^1,10, Medland SE², McGrath J^1,11, Martin NG^#2, Hickie IB^#4, Gillespie NA^#2,12.

Abstract

PURPOSE:

The Nineteen and Up study (19Up) assessed a range of mental health and behavioural problems and associated risk factors in a genetically informative Australian cohort of young adult twins and their non-twin siblings. As such, 19Up enables detailed investigation of genetic and environmental pathways to mental illness and substance misuse within the Brisbane Longitudinal Twin Sample (BLTS).

PARTICIPANTS:

Twins and their non-twin siblings from Queensland, Australia; mostly from European ancestry. Data were collected between 2009 and 2016 on 2773 participants (age range 18-38, 57.8% female, 372 complete monozygotic pairs, 493 dizygotic pairs, 640 non-twin siblings, 403 singleton twins).

FINDINGS TO DATE:

A structured clinical assessment (Composite International Diagnostic Interview) was used to collect lifetime prevalence of diagnostic statistical manual (4th edition) (DSM-IV) diagnoses of major depressive disorder, (hypo)mania, social anxiety, cannabis use disorder, alcohol use disorder, panic disorder and psychotic symptoms. Here, we further describe the comorbidities and ages of onset for these mental disorders. Notably, two-thirds of the sample reported one or more lifetime mental disorder.In addition, the 19Up study assessed general health, drug use, work activity, education level, personality, migraine/headaches, suicidal thoughts, attention deficit hyperactivity disorder (ADHD) symptomatology, sleep-wake patterns, romantic preferences, friendships, familial environment, stress, anorexia and bulimia as well as baldness, acne, asthma, endometriosis, joint flexibility and internet use.The overlap with previous waves of the BLTS means that 84% of the 19Up participants are genotyped, 36% imaged using multimodal MRI and most have been assessed for psychological symptoms at up to four time points. Furthermore, IQ is available for 57%, parental report of ADHD symptomatology for 100% and electroencephalography for 30%.

FUTURE PLANS:

The 19Up study complements a phenotypically rich, longitudinal collection of environmental and psychological risk factors. Future publications will explore hypotheses related to disease onset and development across the waves of the cohort. A follow-up study at 25+years is ongoing.

 

 

 

Int J Surg Pathol. 2018 Mar 1:1066896918763547. doi: 10.1177/1066896918763547. [Epub ahead of print]

Ovarian Clear Cell Adenofibroma of Low Malignant Potential Developing Into Clear Cell Adenocarcinoma.

Yin Z¹, Peters S¹, Chokshi R¹, Heller D¹.

 

Abstract

Ovarian clear cell adenofibroma is uncommon, and borderline clear cell adenofibroma (low malignant potential) is extremely rare. Borderline clear cell adenofibromas may represent the precursor lesion of clear cell adenocarcinoma of the ovary, but this has not been established. We present a case of a woman in her mid-50s with a clear cell adenofibroma ranging from benign to borderline to frankly invasive. While some clear cell adenocarcinomas are thought to arise from endometriosis, this range of findings supports the theory that some ovarian clear cell adenocarcinomas originate from borderline tumors.

 

 

 

Gynecol Obstet Fertil Senol. 2018 Mar 15. pii: S2468-7189(18)30063-1. doi: 10.1016/j.gofs.2018.02.031. [Epub ahead of print]

Nerve sparing techniques in deep endometriosis surgery to prevent urinary or digestive functional disorders: Techniques and results: CNGOF-HAS Endometriosis Guidelines.

Rabischong B¹, Botchorishvili R², Bourdel N², Curinier S², Campagne-Loiseau S², Pouly JL², Canis M².

Abstract

OBJECTIVES:

To evaluate the feasibility and functional urinary and digestive results of nerve sparing techniques in endometriosissurgery.

METHODS:

A research on the medline/pubmed database using specific keywords (nerve sparing, endometriosis, pelvic nerves) identified 7 publications among about 50 whose purpose was to describe the feasibility, the techniques and the functional results of nerve preservation in this indication. Among them there are: 2 uncontrolled retrospective studies, 3 prospective non-randomized studies, a meta-analysis and a review of the literature.

RESULTS:

Nerve preservation requires a perfect knowledge of the anatomy of the pelvic autonomic system. The laparoscopic approach is preferred by the different authors due to its anatomical advantage. The feasibility of this technique seems to be demonstrated despite certain limitations in the different studies and depending of the retroperitoneal extension of the lesions. When feasible, it is likely to significantly improve postoperative urinary function (urinary retention) compared to a conventional technique. It is observed no difference regarding digestive function.

CONCLUSIONS:

Nerve sparing in this indication is a technique the feasibility of which has been demonstrated and is subject to the topography and extent of the disease. In the absence of invasion or entrapment of pelvic autonomic nerves by endometriosis, this technique improves postoperative voiding function (NP3). During pelvic surgery for endometriosis, it is recommended to identify and preserve autonomic pelvic nerves whenever possible (GradeC).

 

 

 

Gynecol Obstet Fertil Senol. 2018 Mar 15. pii: S2468-7189(18)30053-9. doi: 10.1016/j.gofs.2018.02.021.

First line management without IVF of infertility related to endometriosis: Result of medical therapy? Results of ovarian superovulation? Results of intrauterine insemination? CNGOF-HAS Endometriosis Guidelines.

Boujenah J¹, Santulli P², Mathieu-d’Argent E³, Decanter C⁴, Chauffour C⁵, Poncelet P⁶.

Abstract

INTRODUCTION:

Using the structured methodology of French guidelines (HAS-CNGOF), the aim of this chapter was to formulate good practice points (GPP), in relation to optimal non-ART management of endometriosis related to infertility, based on the best available evidence in the literature.

MATERIALS AND METHODS:

This guideline was produced by a group of experts in the field including a thorough systematic search of the literature (from January 1980 to March 2017). Were included only women with endometriosisrelated to infertility. For each recommendation, a grade (A-D, where A is the highest quality) was assigned based on the strength of the supporting evidence.

RESULTS:

Management of endometriosis related to infertility should be multidisciplinary and take account into the pain, the global evaluation of infertile couple and the different phenotypes of endometriotic lesions (good practice point). Hormonal treatment for suppression of ovarian function should not prescribe to improve fertility (grade A). After laproscopy for endometriosis related to infertility, the Endometriosis Fertility Index should be used to counsel patients regarding duration of conventional treatments before undergoing ART (grade C). After laparoscopy surgery for infertile women with AFS/ASRM stage I/II endometriosis or superficial peritoneal endometriosis, controlled ovarian stimulation with or without intrauterine insemination could be used to enhance non-ART pregnancy rate (grade C). Gonadotrophins should be the first line therapy for the stimulation (grade B). The number of cycles before referring ART should not exceed up to 6 cycles (good practice point). No recommendation can be performed for non-ART management of deep infiltrating endometriosis or endometrioma, as suitable evidence is lacking.

DISCUSSION AND CONCLUSION:

Non-ART management is a possible option for the management of endometriosisrelated to infertility. Endometriosis Fertilty Index could be a useful tool for subsequent postoperative fertility management. Controlled ovarian stimulation can be proposed.

Copyright © 2018 Elsevier Masson SAS. All rights reserved.

 

 

 

Best Pract Res Clin Obstet Gynaecol. 2018 Feb 15. pii: S1521-6934(18)30035-X. doi: 10.1016/j.bpobgyn.2018.01.017. [Epub ahead of print]

Perimenopausal management of ovarian endometriosis and associated cancer risk: When is medical or surgical treatment indicated?

Vercellini P¹, Viganò P², Buggio L³, Makieva S⁴, Scarfone G⁵, Cribiù FM⁶, Parazzini F⁷, Somigliana E⁸.

 

Abstract

In women with endometriosis, the lifetime risk of ovarian cancer is increased from 1.4% to about 1.9%. The risk of clear cell and endometrioid ovarian cancer is, respectively, tripled and doubled. Atypical endometriosis, observed in 1-3% of endometriomas excised in premenopausal women, is the intermediate precursor lesion linking typical endometriosis and clear cell/endometrioid tumors. Prolonged oral contraceptive use is associated with a major reduction in ovarian cancer risk among women with endometriosis. Surveillance ± progestogen treatment or surgery should be discussed in perimenopausal women with small, typical endometriomas. In most perimenopausal women with a history of endometriosis but without endometriomas, surveillance instead of risk-reducing bilateral salpingo-oophorectomy seems advisable. Risk-reducing salpingo-oophorectomy might benefit patients at particularly increased risk, but the evidence is inconclusive. Risk profiling models and decision aids may assist patients in their choice. Screening of the general perimenopausal population to detect asymptomatic endometriomas is unlikely to reduce disease-specific mortality.

 

 

 

J Pediatr Adolesc Gynecol. 2018 Mar 15. pii: S1083-3188(18)30181-5. doi: 10.1016/j.jpag.2018.03.004. [Epub ahead of print]

Long-Term Effects of Gonadotropin-Releasing Hormone Agonists and Add-Back in Adolescent Endometriosis.

Gallagher JS¹, Missmer SA², Hornstein MD³, Laufer MR⁴, Gordon CM⁵, DiVasta AD⁶.

Abstract

STUDY OBJECTIVE:

To explore the potential occurrence of long-term side effects and tolerability of gonadotropin-releasing hormone agonist (GnRHa) plus 2 different add-back regimens in adolescent patients with endometriosisDESIGN: Follow-up questionnaire sent in 2016 to patients who participated in a drug trial between 2008-2012 SETTING: Tertiary care center in Boston, MA.

PARTICIPANTS:

Females with surgically confirmed endometriosis (n=51) who enrolled in a GnRHa plus add-back trial as adolescents INTERVENTIONS: Leuprolide depot 11.25 mg intramuscular injection every 3 month, plus oral norethindrone acetate 5 mg daily or oral norethindrone acetate 5 mg daily plus oral conjugated equine estrogens 0.625 mg daily.

MAIN OUTCOME MEASURE(S):

Side effects during and after treatment, irreversible side effects, changes in pain, overall satisfaction RESULTS: The response rate was 61%. Almost all (96%) reported side effects during treatment; 80% reported side effects lasting > 6 months after stopping treatment. Almost half (45%) reported side effects they considered irreversible, including memory loss, insomnia, and hot flashes. Despite side effects, subjects rated GnRHa plus add-back as the most effective hormonal medication for treating endometriosis pain; two thirds (16/25) would recommend it to others. More subjects who received a modified two drug add-back regimen versus standard one drug add-back would recommend GnRHa and felt it was the most effective hormonal medication.

CONCLUSION:

Subjects felt GnRHa plus add-back was effective and would recommend it to others, despite significant side effects. Those who received two drug add-back reported more success than those who received standard add-back. A subset of patients reported irreversible side effects.

 

 

 

J Minim Invasive Gynecol. 2018 Mar 15. pii: S1553-4650(18)30158-4. doi: 10.1016/j.jmig.2018.02.023. [Epub ahead of print]

Near-Infrared Imaging with Indocyanine Green for Detection of EndometriosisLesions (Gre-Endo Trial): a Pilot Study.

Cosentino F¹, Vizzielli G², Turco LC³, Fagotti A², Cianci S², Vargiu V², Zannoni GF⁴, Ferrandina G², Scambia G³.

Abstract

STUDY OBJECTIVE:

To evaluate near-infrared radiation imaging with intravenous indocyanine green (NIR-ICG) during laparoscopic intervention to identify endometriosis lesions.

DESIGN:

A single center, prospective, single-arm pilot study (Canadian Task Force classification II-2).

SETTING:

An academic tertiary care and research center.

PATIENTS:

Twenty-seven patients with symptomatic endometriosis were enrolled.

INTERVENTIONS:

Patients underwent laparoscopic surgery using a laparoscopic system prototype with NIR-ICG.

MEASUREMENTS AND MAIN RESULTS:

A total of 116 suspected endometriosis lesions were removed from 27 patients. One hundred lesions had already been visualized in white light imaging by an expert surgeon; the remaining 16 were detected and removed using NIR-ICG. A total of 111 specimens were positive for endometriosis pathology. Positive predictive value of 95% and 97.8% and negative predictive value of 86.2% and 82.3% were found by white light imaging and NIR-ICG, respectively with sensitivity of 85.6% and 82% and specificity of 95.2% and 97.9%, also respectively.

CONCLUSIONS:

Near-infrared radiation imaging following intravenous injection of ICG may be a tool for intraoperative diagnosis, confirmation of visible endometriosis lesions, and a marker for identifying occult endometriosis. Further prospective studies with a larger population sample are warranted to validate these encouraging preliminary results.

Copyright © 2018. Published by Elsevier Inc.

 

 

 

Radiol Case Rep. 2017 Oct 13;13(1):81-85. doi: 10.1016/j.radcr.2017.09.003. eCollection 2018 Feb.

Catamenial pneumothorax caused by thoracic endometriosis.

Maniglio P¹, Ricciardi E², Meli F¹, Vitale SG³, Noventa M⁴, Vitagliano A⁴, Valenti G⁵, La Rosa VL⁶, Laganà AS³, Caserta D¹.

Abstract

BACKGROUND:

Thoracic endometriosis syndrome is a rare form of extrapelvic endometriosis characterized by the presence of functioning endometrial tissue in pleura, lung parenchyma, and airways, associated with a high rate of infertility.

CASE REPORT:

We have reported a case of successful management and treatment of thoracic endometriosissyndrome that occurred in a 37-year-old female patient. She underwent thoracoscopic resection of the lesion. During follow-up, we revealed the recurrence of a previously surgically treated thoracic endometriosis. She was initially treated with a gonadotropin-releasing hormone agonist; subsequently this was replaced by a prophylactic treatment with Dienogest.

CONCLUSION:

The diagnosis of thoracic endometriosis is challenging. The first line of treatment is medical, whereas the surgical treatment is performed secondly. Moreover, surgical treatment can lead to a significant rate of recurrence, often reduced by a coadjutant medical treatment.

 

 

 

Rev Bras Ginecol Obstet. 2018 Mar 19. doi: 10.1055/s-0038-1626700. [Epub ahead of print]

Ascites and Encapsulating Peritonitis in Endometriosis: a Systematic Review with a Case Report.

Magalhães TF¹, Augusto KL^1,2, Mota LP³, Costa ARD³, Puster RA³, Bezerra LRPS¹.

 

Abstract

Endometriosis can have several different presentations, including overt ascites and peritonitis; increased awareness can improve diagnostic accuracy and patient outcomes. We aim to provide a systematic review and report a case of endometriosis with this unusual clinical presentation. The PubMed/MEDLINE database was systematically reviewed until October 2016. Women with histologically-proven endometriosis presenting with clinically significant ascites and/or frozen abdomen and/or encapsulating peritonitis were included; those with potentially confounding conditions were excluded. Our search yielded 37 articles describing 42 women, all of reproductive age. Ascites was mostly hemorrhagic, recurrent and not predicted by cancer antigen 125 (CA-125) levels. In turn, dysmenorrhea, dyspareunia and infertility were not consistently reported. The treatment choices and outcomes were different across the studies, and are described in detail. Endometriosis should be a differential diagnosis of massive hemorrhagic ascites in women of reproductive age.

 

 

 

Clin Biochem. 2018 Mar 16. pii: S0009-9120(18)30220-0. doi: 10.1016/j.clinbiochem.2018.03.012. [Epub ahead of print]

Fertility and infertility: Definition and epidemiology.

Mélodie VB¹, Christine W².

 

Abstract

Infertility is a disease characterized by the failure to establish a clinical pregnancy after 12 months of regular and unprotected sexual intercourse. It is estimated to affect between 8 and 12% of reproductive-aged couples worldwide. Males are found to be solely responsible for 20-30% of infertility cases but contribute to 50% of cases overall. Secondary infertility is the most common form of female infertility around the globe, often due to reproductive tract infections. The three major factors influencing the spontaneous probability of conception are the time of unwanted non-conception, the age of the female partner and the disease-related infertility. The chance of becoming spontaneously pregnant declines with the duration before conception. The fertility decline in female already starts around 25-30 years of age and the median age at last birth is 40-41 years in most studied populations experiencing natural fertility. The disease-related infertility may affect both genders or be specific to one gender. The factors affecting both genders’ fertility are hypogonadotrophic hypogonadism, hyperprolactinemia, disorders of ciliary function, cystic fibrosis, infections, systemic diseases and lifestyle related factors/diseases. Premature ovarian insufficiency, polycystic ovary syndrome, endometriosis, uterine fibroids and endometrial polyps may play a role in female infertility. Male infertility may be due to testicular and post-testicular deficiencies. Semen decline that has been observed over the years, endocrine disrupting chemicals and consanguinity are other factors that may be involved.

 

 

 

FASEB J. 2018 Mar 20:fj201701382RR. doi: 10.1096/fj.201701382RR. [Epub ahead of print]

EGFR-mediated matrix metalloproteinase-7 up-regulation promotes epithelial-mesenchymal transition via ERK1-AP1 axis during ovarian endometriosisprogression.

Chatterjee K¹, Jana S^1,2, DasMahapatra P³, Swarnakar S¹.

 

Abstract

Endometriosis, characterized by extrauterine development of endometrial glands and stroma, is associated with increased risk of ovarian cancer development. In the present study, we investigated the role of matrix metalloproteinase-7 (MMP-7) on epithelial-mesenchymal transition (EMT) during ovarian endometriosis ( N = 40) progression. We found that the expressions of EMT markers such as vimentin, slug, and N-cadherin were significantly elevated in late stages of ovarian endometriosis compared with those found in early stages. In addition, the activity and expression of ectopic MMP-7 were significantly higher in the late stages of endometriosis. In vitro studies revealed that increased expression of MMP-7 as well as epidermal growth factor (EGF), which was significantly elevated in severe stages of ovarian endometriosis, induced EMT in endocervical epithelial cells (End1/E6E7). Silencing the MMP-7 transcripts using small interfering RNA attenuated EMT responses, whereas treatment with recombinant active MMP-7 promoted EMT by cleaving E-cadherin. In addition, EGF receptor (EGFR) inhibitor treatments regressed endometriotic lesions and decreased MMP-7 activities in a mouse model of endometriosis. Chromatin immunoprecipitation assay identified EGFR-mediated ERK1 and activator protein 1 signaling for the transcriptional activation of MMP-7 in End1/E6E7 epithelial cells.-Chatterjee, K., Jana, S., DasMahapatra, P., Swarnakar, S. EGFR-mediated matrix metalloproteinase-7 up-regulation promotes epithelial-mesenchymal transition via ERK1-AP1 axis during ovarian endometriosis progression.