Adenoid cystic carcinoma of Bartholin's gland, a case report with genomic data and literature review.

Adenoid cystic carcinoma of the Bartholin's gland (ACCBG) is a rare, slowly but aggressive malignancy. We reported the case of a 31-year-old woman who was treated by local excision and then hemi-vulvectomy, with positive margins and perineural invasion. Radiation therapy (RT) was then performed delivering 45Gy in 25 fractions in bilateral inguinal lymph nodes and 64.8Gy in 36 fractions on the vulvar area. After 30 months, there was no local relapse (LR) but the patient presented a histologically documented lung recurrence. Genomic profiling of the tumor showed a MYB-NFIB fusion transcript and a somatic mutation of PLCG1. A treatment by Lenvatinib was started. We conducted a literature review of 100 published cases. Patients were mainly treated by radical vulvectomy (30%), hemi-vulvectomy (17%), wide or local excision (21% and 24%, respectively) or other. Forty-four percent of patients received postoperative RT, more frequently in case of positive margin (71.9% versus 29.5%). RT may reduce the risk of LR regardless of margin status, with 15.4% vs. 41.9% of LR with or without RT, respectively, in patients with negative margins, and 13% vs. 33.3% of LR with or without RT, respectively, in patients with positive margins. The risk of relapse of any type was 40.9% in patients who received adjuvant RT vs. 48.2% in patients who did not. Median time to relapse was 24 months (range 6-156 months). The most frequent metastatic sites were lung (76.7%) and bone (26.7%). Optimal treatment for ACCBG is still not clearly defined but pooling the data from published case report help us better understand this rare disease and help in the therapeutic decision.

Associated ileocaecal location is a marker for greater severity of low rectal endometriosis.

OBJECTIVE: To determine whether ileocaecal endometriosis (ICE) is a marker for low rectal endometriosis (LRE) severity. DESIGN: Retrospective cohort study. SETTING: France. POPULATION AND SAMPLE: Analysis of 375 colorectal resections performed in women undergoing complete surgery for LRE from January 1995 to December 2015 in a university centre for endometriosis. METHODS: Univariate and multivariate analysis of anatomical, postoperative clinical, and long-term outcomes according to presence of ICE. MAIN OUTCOMES AND MEASURES: Mean number and type of deep infiltrating endometriosis (DIE) lesions, the existence of an associated endometrioma, and mean total American Society for Reproductive Medicine (ASRM) score. RESULTS: The prevalence of ICE was 25.6%. Primary end-point data showed that women with ICE had a significantly higher adjusted number of DIE lesions (OR = 1.43, 95% CI 1.02-3.03; P = 0.048), higher prevalence of endometriomas (OR = 1.91, 95% CI 1.04-3.51; P = 0.044), more associated DIE sigmoid lesions (OR = 2.12, 95% CI 1.07-3.91; P = 0.025), and a higher mean total ASRM score (OR = 2.07, 95% CI 1.12-4.14; P = 0.025). Women with ICE resected during the surgical procedure for LRE did not have more adverse postoperative clinical outcomes than ICE-negative patients. CONCLUSION: Ileocaecal endometriosis was significantly associated with greater LRE severity. In a complete surgical resection strategy, combining resection of ICE and LRE did not appear to increase postoperative rates of complications, morbidity or recurrence, nor did it seem to impair long-term clinical outcomes. TWEETABLE ABSTRACT: In women with low rectal endometriosis, 25% have an associated ileocaecal location that is a marker for severity.

Management of endometriosis: CNGOF/HAS clinical practice guidelines - Short version.

First-line diagnostic investigations for endometriosis are physical examination and pelvic ultrasound. The second-line investigations are: targeted pelvic examination performed by an expert clinician, transvaginal ultrasound performed by an expert physician sonographer (radiologist or gynaecologist), and pelvic MRI. Management of endometriosis is recommended when the disease has a functional impact. Recommended first-line hormonal therapies for the management of endometriosis-related pain are combined hormonal contraceptives (CHCs) or the 52mg levonorgestrel-releasing intrauterine system (IUS). There is no evidence base on which to recommend systematic preoperative hormonal therapy solely to prevent surgical complications or facilitate surgery. After surgery for endometriosis, a CHC or 52mg levonorgestrel-releasing IUS is recommended as first-line treatment when pregnancy is not desired. In the event of failure of the initial treatment, recurrence, or multiorgan involvement, a multidisciplinary team meeting is recommended, involving physicians, surgeons and other professionals. A laparoscopic approach is recommended for surgical treatment of endometriosis. HRT can be offered to postmenopausal women who have undergone surgical treatment for endometriosis. Antigonadotrophic hormonal therapy is not recommended for patients with endometriosis and infertility to increase the chances of spontaneous pregnancy, including postoperatively. Fertility preservation options must be discussed with patients undergoing surgery for ovarian endometriomas.

[Epidemiology and diagnosis strategy: CNGOF-HAS Endometriosis Guidelines]. / Épidémiologie et stratégie diagnostique, RPC Endométriose CNGOF­HAS.

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.

[Management of assisted reproductive technology (ART) in case of endometriosis related infertility: CNGOF-HAS Endometriosis Guidelines]. / Stratégies de prise en charge de l'infertilité en assistance médicale à la procréation dans un contexte d'endométriose, RPC Endométriose, CNGOF-HAS.

The management of endometriosis related infertility requires a global approach. In this context, the prescription of an anti-gonadotropic hormonal treatment does not increase the rate of non-ART (assisted reproductive technologies) pregnancies and it is not recommended. In case of endometriosis related infertility, the results of IVF management in terms of pregnancy and birth rates are not negatively affected by the existence of endometriosis. Controlled ovarian stimulation during IVF does not increase the risk of endometriosis associated symptoms worsening, nor accelerate the intrinsic progression of endometriosis and does not increase the rate of recurrence. However, in the context of IVF management for women with endometriosis, pre-treatment with GnRH agonist or with oestrogen/progestin contraception improve IVF outcomes. There is currently no evidence of a positive or negative effect of endometriosis surgery on IVF outcomes. Information on the possibilities of preserving fertility should be considered, especially before surgery.

[Definition, description, clinicopathological features, pathogenesis and natural history of endometriosis: CNGOF-HAS Endometriosis Guidelines]. / Définition, description, formes anatomo-cliniques, pathogenèse et histoire naturelle de l'endométriose, RPC Endométriose CNGOF-HAS.

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.

[Management of endometriosis: CNGOF-HAS practice guidelines (short version)]. / Prise en charge de l'endométriose : recommandations pour la pratique clinique CNGOF-HAS (texte court).

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 echographist, 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 with 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.

Recent insights on the genetics and epigenetics of endometriosis.

Endometriosis is a gynecologic disease affecting up to 10% of the women and a major cause of pain and infertility. It is characterized by the implantation of functional endometrial tissue at ectopic positions generally within the peritoneum. This complex disease has an important genetic component with a heritability estimated at around 50%. This review aims at providing recent insights into the genetic bases of endometriosis, and presents a detailed overview of evidence of epigenetic alterations specific to this disease. In the future, these alterations may constitute therapeutic targets for pharmacological compounds able to modify the epigenetic code.

Endometriosis-related infertility: ovarian endometrioma per se is not associated with presentation for infertility.

STUDY QUESTION: Is there an association between the endometriosis phenotype and presentation with infertility? SUMMARY ANSWER: In a population of operated patients with histologically proven endometriosis, ovarian endometrioma (OMA) per se is not associated with an increased risk of presentation with infertility, while previous surgery for endometriosis was identified as a risk factor for infertility. WHAT IS KNOWN ALREADY: The increased prevalence of endometriosis among subfertile women indicates that endometriosis impairs reproduction for reasons that are not completely understood. STUDY DESIGN, SIZE, DURATION: This was an observational, cross-sectional study using data prospectively collected in all non-pregnant patients aged between 18 and 42 years, who were surgically explored for benign gynaecological conditions at our institution between January 2004 and March 2013. For each patient, a standardized questionnaire was completed during a face-to-face interview conducted by the surgeon during the month preceding surgery. PARTICIPANTS/MATERIALS, SETTING, METHODS: Surgery was performed in 2208 patients, of which 2066 signed their informed consent. Of the 1059 women with a visual diagnosis of endometriosis, 870 had histologically proven endometriosis and complete treatment for their endometriotic lesions, including 307 who presented with infertility. Univariate analysis and multiple logistic regression analysis were performed to determine factors associated with infertility. MAIN RESULTS AND THE ROLE OF CHANCE: The following variables were identified as risk factors for endometriosis-related infertility: age >32 years (odds ratio [OR] = 1.9; 95% confidence interval [CI]: 1.4-2.4), previous surgery for endometriosis (OR = 1.9; 95% CI: 1.3-2.2), as well as peritoneal superficial endometriosis (OR = 3.1; 95% CI: 1.9-4.9); Conversely, previous pregnancy was associated with a lower rate of infertility (OR = 0.7; 95% CI: 0.6-0.9 and OR = 0.6; 95% CI: 0.4-0.9, respectively). OMA is not selected as a significant risk factor for infertility. LIMITATIONS, REASON FOR CAUTION: The selection of our study population was based on a surgical diagnosis. We cannot exclude that infertile women with OMA associated with a diminished ovarian reserve, as assessed during their infertility work-up, were referred less frequently to surgery and might therefore be underrepresented. In addition we cannot exclude that our group of infertile women present associated other causes of infertility. WIDER IMPLICATIONS OF THE FINDINGS: Identification of risk and preventive factors of endometriosis-related infertility can help improve clinical and surgical management of endometriosis in the setting of infertility. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: None.

Fusion imaging for evaluation of deep infiltrating endometriosis: feasibility and preliminary results.

OBJECTIVE: Magnetic resonance imaging (MRI) and ultrasound scanning complement each other in screening for and diagnosis of endometriosis. Fusion imaging, also known as real-time virtual sonography, is a new technique that uses magnetic navigation and computer software for the synchronized display of real-time ultrasound and multiplanar reconstructed MR images. Our aim was to evaluate the feasibility and ability of fusion imaging to assess the main anatomical sites of deep infiltrating endometriosis (DIE) in patients with suspected active endometriosis. METHODS: This prospective study was conducted over a 1-month period in patients referred to a trained radiologist for an ultrasound-based evaluation for endometriosis. Patients with a prior pelvic MRI examination within the past year were offered fusion imaging, in addition to the standard evaluation. All MRI examinations were performed on a 1.5-T MRI machine equipped with a body phased-array coil. The MRI protocol included acquisition of at least two fast spin-echo T2-weighted orthogonal planes. The Digital Imaging Communications in Medicine dataset acquired at the time of the MRI examination was loaded into the fusion system and displayed together with the ultrasound image on the same monitor. The sets of images were then synchronized manually using one plane and one anatomical reference point. The ability of this combined image to identify and assess the main anatomical sites of pelvic endometriosis (uterosacral ligaments, posterior vaginal fornix, rectum, ureters and bladder) was evaluated and compared with that of standard B-mode ultrasound and MRI. RESULTS: Over the study period, 100 patients were referred for ultrasound examination because of endometriosis. Among them were 20 patients (median age, 35 (range, 27-49) years) who had undergone MRI examination within the past year, with a median (range) time interval between MRI and ultrasound examination of 171 (1-350) days. All 20 patients consented to undergo additional evaluation by fusion imaging. However, in three (15%) cases, fusion imaging was not technically possible because of changes since the initial MRI examination resulting from either interval surgery (n = 2; 10%) or pregnancy (n = 1; 5%). Data acquisition, matching and fusion imaging were performed in under 10 min in each of the other 17 cases. The overall ability of each technique to identify and assess the main anatomical landmarks of endometriosis was as follows: uterosacral ligaments: ultrasound, 88% (30/34); MRI, 100% (34/34); fusion imaging, 100% (34/34); posterior vaginal fornix: ultrasound, 88% (30/34); MRI, 100% (34/34); fusion imaging, 100% (34/34); rectum: ultrasound, 100% (17/17); MRI, 82.3% (14/17); fusion imaging, 100% (17/17); ureters: ultrasound, 0%; MRI, 100% (34/34); fusion imaging, 100% (34/34); and bladder: ultrasound, 100%; MRI, 100%; fusion imaging, 100%. CONCLUSION: Fusion imaging is feasible for the assessment of endometriotic lesions. Because it combines information from both ultrasound and MRI techniques, fusion imaging allows better identification of the main anatomical sites of DIE and has the potential to improve the performance of ultrasound and MRI examination.

Management of presumed benign ovarian tumors: updated French guidelines.

Transvaginal pelvic ultrasound is the first-line imaging examination for presumed benign ovarian tumors (PBOT) in adult women (Grade A). Ultrasound is sufficient for characterizing a unilocular anechoic cyst smaller than 7cm (Grade A). Magnetic resonance imaging is the recommended second-line investigation for indeterminate masses or masses larger than 7cm (Grade B). Serum CA-125 assay is not recommended for first-line diagnosis in adult women (Grade C). In women with a unilocular anechoic cyst, hormone therapy is ineffective and not recommended (Grade A). Ultrasound-guided aspiration is not recommended (Grade B). Abstention is an option in adult women with a unilocular asymptomatic anechoic cyst smaller than 10cm and no history of cancer (Grade B). If symptoms develop, laparoscopy is the gold standard for surgical treatment of PBOT (Grade A). Conservative surgical treatment (cystectomy) should be preferred to oophorectomy in pre-menopausal women without a previous history of cancer (Grade C). In cases of suspected adnexal torsion, laparoscopic surgical exploration is recommended (Grade B). Conservative treatment or detorsion without oophorectomy is recommended for pre-menopausal women regardless of the estimated torsion duration and macroscopic appearance of the ovary (Grade B). During pregnancy, expectant management is recommended for unilocular asymptomatic anechoic cysts smaller than 6cm (Grade C).

[Endometriosis: increasing concentrations of serum interleukin-1ß and interleukin-1sRII is associated with the deep form of this pathology]. / Endométriose: l'augmentation des concentrations d'interleukine-1ß et d'interleukine-1sRII dans le sérum est associée à la forme profonde de cette pathologie.

OBJECTIVES: To assess interleukin-1ß (IL-1ß) and its inhibitory soluble interleukin-1 receptor type II (IL-1sRII) levels into the serum of patients with various forms of endometriosis and normal women, and investigate the correlation with disease activity. PATIENTS AND METHODS: In this prospective laboratory study (2005-2010), 510 women with histologically proven endometriosis and 93 endometriosis-free controls have been enrolled. Laparoscopic complete exploration of the abdominopelvic cavity and blood samples have been performed in each patient. For each serum, IL-1ß and IL-1sRII have been evaluated using Elisa. RESULTS: IL-1ß and IL-1sRII have been respectively detectable in 64% and 54.6% of serum samples from all 603 women studied. IL-1ß was higher in women with deep infiltrating endometriosis (DIE) (mean 10.0pg/mL [0.005-416.2]) than in endometriosis-free women (mean 0.5pg/mL [0.01-1.7], P<0.01) or in women with superficial endometriosis (SUP) (mean 0.6pg/mL [0.1-2.9], P<0.01). Also, IL-1sRII was higher in DIE (mean 236.7pg/mL [0.9-6975]) than in the witness group (mean 85.0pg/mL [1-235.2], P<0.05) or in SUP (mean 85.1pg/mL [0.6-302], P<0.01). CONCLUSION: This study highlights both a marked significant increase in serum IL-1ß and IL-1sRII levels in DIE compared to SUP and normal women and suggests that a defect in the control of IL-1 can impact the pathophysiology of endometriosis.

A clinical score can predict associated deep infiltrating endometriosis before surgery for an endometrioma.

STUDY QUESTION: Is it possible to detect associated deep infiltrating endometriosis (DIE) before surgery for patients operated on for endometriomas using a preoperative clinical symptoms questionnaire? SUMMARY ANSWER: A diagnostic score of DIE associated with endometriomas using four clinical symptoms defined a high-risk group where the probability of DIE was 88% and a low-risk group with a 10% probability of DIE. WHAT IS KNOWN ALREADY: Many clinical symptoms are already known to be associated with DIE but they have not yet been used to build a clinical prediction model. STUDY DESIGN, SIZE, DURATION: We built a diagnostic score of DIE based on a case control study of 326 consecutive patients operated on for an endometrioma between January 2005 and October 2011: 164 had associated DIE (DIE+) and 162 had no DIE (DIE-). We derived the score on a training sample obtained from a random selection of 2/3 of the population (211 patients, 101 DIE+, 110 DIE-), and validated the results on the remaining third (115 patients, 63 DIE+, 52 DIE-). The gold standard for the diagnosis of DIE was based on surgical exploration and histological diagnosis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were consecutive patients aged 18-42 years who underwent surgery for an endometrioma with histological confirmation and complete treatment of their endometriotic lesions: data for these women were extracted from a prospective database including a standardized preoperative questionnaire. On the training dataset, variables associated with DIE in a univariate analysis were introduced in a multiple logistic regression and selected by a backward stepwise procedure and a Jackknife procedure. A diagnostic score of DIE was built with the scaled/rounded coefficients of the multiple regression. Two cut-off values delimitated a high and a low risk group, and their diagnostic accuracy was tested on the validation dataset. MAIN RESULTS AND THE ROLE OF CHANCE: Four variables were independently associated with DIE: visual analogue scale of gastro-intestinal symptoms ≥5 or of deep dyspareunia >5 (adjusted diagnostic odds ratio (aDOR) = 6.0, 95% confidence interval (CI) [2.9-12.1]), duration of pain greater than 24 months (aDOR = 3.8, 95% CI [1.9-7.7]), severe dysmenorrhoea (defined as the prescription of the oral contraceptive pill for the treatment of a primary dysmenorrhoea or the worsening of a secondary dysmenorrhoea) (aDOR = 3.8, 95% CI [1.9-7.6]) and primary or secondary infertility (aDOR = 2.5, 95% CI [1.2-4.9]). The sum of these variables weighted by their rounded/scaled coefficients constituted the score ranging from 0 to 53. A score <13 defined a low-risk group where the probability of DIE was 10% (95% CI [7-15] with a sensitivity of 95% (95% CI [89-98]) and a negative likelihood ratio of 0.1 (95% CI [0.0-0.3]). A score ≥35 defined a high-risk group where the probability of DIE was 88% (95% CI [83-92%]), with a specificity of 94% (95% CI [87-97]), and a positive likelihood ratio of 8.1 (95% CI [3.9-17.0]). The performance of the score was confirmed on the validation dataset with 11% of DIE+ patients having a score <13 (sensibility: 95%) and 90% of DIE+ patients having a score ≥35 (specificity: 94%). LIMITATION, REASONS FOR CAUTION: This study was performed in a department specialized in DIE management. Score accuracy could be different in less specialized centres. WIDER IMPLICATIONS OF THE FINDINGS: This score could have a major clinical impact on the time of diagnosis, the management of DIE and could reduce the cost of investigations by helping to identify high-risk patients, while preserving the quality of care. STUDY FUNDING/COMPETING INTERESTS: The authors have no competing interests to declare. No grant supported the study.

[Urinary functional disorders bound to deep endometriosis and to its treatment: review of the literature]. / Troubles fonctionnels urinaires liés à l'endométriose profonde et à son traitement : revue de la littérature.

Lower urinary tract disorders in case of deep endometriosis are common (up to 50% of patients), although often masked by pelvic pain. They result from damage to the pelvic autonomic nervous system by direct infiltration of these structures by endometriotic lesions or surgical trauma (especially in resection of the uterosacral ligaments, rectum or vagina). These are mainly sensory disturbances and bladder voiding dysfunction. They impact quality of life and could be responsible for long-term complications (recurrent urinary tract infections on a persistent residual urine or pelvic floor disorders due to chronic thrusting). It is therefore important to diagnose and treat early these troubles by well-conducted interviews or standardized questionnaires. Different drug treatments have been proposed, such as cholinergics or prokinetics, but their effectiveness has not been demonstrated yet. Neuromodulation of the superior hypogastric plexus for treatment of refractory atonic bladder with persistent urinary retention after surgery seems promising but should be confirmed by further studies. To date, standard treatment of urinary retention after surgery remains self-catheterization. In terms of prevention, surgical nerve sparing techniques have been developed in order to minimize intraoperative injury of pelvic nerve plexus and reduce postoperative morbidity.

[Recurrence of pain after surgery for deeply infiltrating endometriosis: How does it happen? How to manage?]. / Récidive de la douleur après chirurgie pour endométriose profonde : pourquoi ? Que faire ?

Recurrence of deep endometriosis remains a major issue in the management of endometriosis. The main cause for recurrence appears to be an incomplete excisional surgery. Therefore, the goal of the primary surgery should be the complete resection of all endometriotic lesions. If surgical skills cannot meet this objective it seems preferable to refer the patient to a center with a recognized expertise in this field rather than performing an incomplete surgery. It seems also possible to tailor the indications according to the symptoms, especially when endometriosis affects the bladder in association with an asymptomatic vaginal and/or rectal involvement. This strategy does not increase the rate of recurrence. Postoperative medical treatment based on ovarian function suppression is attractive as it diminishes the recurrence rate. Facing the recurrence, appropriate assessment of the benefit risk balance must be performed. Medical treatment is an option. When surgery is chosen, it seems interesting to discuss carefully the indication of hysterectomy with bilateral oophorectomy, especially for women over 40 years old with no desire for pregnancy and/or symptomatic adenomyosis. Risks of induced ovarian castration must be taken into account.

[Surgical treatments of presumed benign ovarian tumors]. / Traitements chirurgicaux des tumeurs ovariennes présumées bénignes.

The surgical management of presumed benign ovarian tumors (PBOT) must ensure complete removal of the cyst, reduce the risk of recurrence (especially in case of endometrioma), prevent any risk of tumor dissemination, and must preserve healthy ovarian tissue. Asymptomatic PBOT should not be punctured. Expectation is preferable to puncture. Laparoscopy is the gold standard for surgical treatment. Single-port laparoscopy is feasible and being evaluated. Peritoneal exploration and peritoneal cytology are conventionally performed. Ovarian cystectomy, oophorectomy and salpingo-oophorectomy are the standard techniques. Suture after cystectomy is not recommended. The extraction of the cyst using an endoscopic bag is recommended. Peritoneal washing after surgery is recommended. The use of anti-adhesions barriers is not recommended routinely. In case of dermoid cyst, cystectomy by mesial incision may decrease the risk of intraoperative rupture. In case of endometrioma, the intraperitoneal cystectomy is recommended as first-line surgery. Exclusive bipolar coagulation should be avoided because of increased risk of recurrence and lower pregnancy rates. There is no argument to support the use of plasma energy and CO2 laser in the treatment of endometriomas. Ethanol sclerotherapy may be proposed in patients with recurrent endometriomas after surgery and referred to medically assisted procreation, although there is no comparative trial with cystectomy.

[Endometriosis-associated ovarian cancers: pathogenesis and consequences on daily practice]. / Les cancers de l'ovaire associés à l'endométriose : physiopathologie et conséquences sur la pratique clinique.

Endometriosis is considered as a tumor-like lesion under the World Health Organization (WHO) classification of ovarian tumors. Data from large cohort and case-control studies indicate that patients with a history of endometriosis have an increased risk of ovarian cancer. Recent findings suggest an association between endometriosis and the entire type 1 ovarian tumors group including clear-cell, endometrioid and low-grade serous carcinomas. However, current evidence is lacking to draw definitive conclusion whether this association represents causality or the sharing of common risk factors. Nevertheless, assumption that endometriosis could be a precursor of malignancy raises many issues about serial screening, surgical management and surveillance of endometriosis. Beyond these concerns, endometriosis-associated ovarian cancers seem to be a genuine clinical entity as regards clinicopathological features. In view of the high incidence of endometriosis (10 % of women of childbearing age), the low incidence of endometriosis-associated ovarian cancers and the psychological consequences for those women, systematic screening and surgical exploration seem very questionable in this context.

Infertility and endometriosis: a need for global management that optimizes the indications for surgery and ART.

Endometriosis causes pelvic pain and infertility. Infertility results from effects of endometriosis exerted in the pelvic cavity, in the ovaries and/or on the uterus. Medical treatment effective on pain and at preventing disease recurrence following surgery is of no use for improving the chances of conceiving naturally. Surgery however improves the chances of conceiving in the 12-18 months afterward. Endometriosis through extension of the disease to the ovaries may harm ovarian response to COS needed in ART. Surgery for endometrioma(s) may further reduce ovarian responses to COS in case of endometriosis. Remarkably however, reduced ovarian responses due to endometriosis are not necessarily associated with reduced oocyte quality and ART outcome. Pre-ART treatment with oral contraceptives (OC) improves ART outcome in case of ovarian endometriosis particularly, if endometriomas are present at the time of oocyte retrieval. This measure requires however that a proper OC-FSH/hMG interval is respected and that "LH" effects are provided during the ovarian stimulation, using either hMG or small doses of hCG. These latter precautions prevent the adverse outcome reported in case of pre-ART use of OC when ovarian stimulation is conducted using r-FSH exclusively.

[Neurotrophins and pain in endometriosis]. / Neurotrophines et douleur: étude d'expression et de corrélation dans l'endométriose.

OBJECTIVES: To evaluate the expression of five members of the neurotrophins family in ovarian endometriotic cyst (endometrioma) (OMA), compared to eutopic endometrium (EE) and to examine the correlation between the levels of induction and the pain intensity. PATIENTS AND METHODS: Twelve Caucasian women in luteal phase, operated for painful stage IV endometriosis were assigned to 2 groups according to a total Visual Analog Scale (tVAS) score above 15 or below 10. tVAS takes into account all VAS scores for dysmenorrhea, deep dyspareunia, non cyclic chronic pelvic pain, gastrointestinal and lower urinary symptoms. Samples of OMA and EE were processed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) for NGF, BDNF, NT-3, NT-4/5 and NTRK2 mRNA expression. Expression levels in OMA were compared to those in EE on one hand and between two groups of 6 mild painful and 6 highly painful patients on the other. RESULTS: All neurotrophins were significantly higher expressed in OMA than in EE, in particular NGF and BDNF (induction ratios: 20.6 and 9.7, respectively). In contrast, no correlation was observed between induction ratios and pain intensity. CONCLUSION AND DISCUSSION: This is the first study reporting an over-expression of all neurotrophins in endometriosis, as only NGF was previously documented. It confirms the central role of this family in the genesis and modulation of pain in endometriosis. Anti-neurotrophin selective therapy might be a promising way of analgesia in the future.