Michele Vignali

Endometrioma Excision and Ovarian Reserve: A Dangerous Relation

Endometrioma is one of the most frequent pathologies in gynecologic surgery. Laparoscopic cyst excision is considered the best treatment in terms of lower recurrence and improved fertility. However, it was recently questioned whether the excision of the endometrioma could decrease the function of the operated ovary and if it could affect the subsequent fertility. Even if a consistent amount of ovarian tissue is unintentionally removed together with the capsule of the cyst, resulting in does not show the follicular pattern observed in working ovaries. Currently, no definitive data clarify whether the damage to the ovarian reserve, observed in patient with endometrioma, is related to the surgical procedure, to the previous presence of the cyst, or both. Electrosurgial coagulation during hemostasis could play an important role in terms of damage to ovarian stroma and vascularization. Particular attention must be paid in presence of bilateral endometriotic cysts. In fact, an increase in premature ovarian failure rate was reported when both the ovaries are involved in surgery. Incase of assisted reproductive techniques, no clear evidence indicates which is the best approach for concomitant endometriotic cyst. On the base of these considerations endometriomas Should be treated only in case of pain, infertility, and in asymptomatic patients if the cyst diameter is greater than 4 cm.

Ovarian endometriosis: from pathogenesis to surgical treatment.

Purpose of review This review analyzes the literature on ovarian endometrioma, examining the controversies on pathogenesis, malignant transformation and surgical therapy. Recent findings Recent literature reflects the necessity of clearly defining the ethiologic and pathologic factors that determine the origin of ovarian endometriosis and explain the increase in the condition with the prospect of developing effective prevention therapy. The possibility that ovarian endometriomas undergo malignant transformation is widely reported in the literature. Recent studies underline the importance of detecting histological differences in endometriosis (hyperplasia and atypia) and several studies of molecular biology support the theory of genetic alterations interfering with malignant transformation of ovarian endometriosis. Summary The surgical approach must take into account all this information and, when the therapy is conservative, complete excision of the disease must be laparoscopically performed without affecting the healthy ovarian tissue.

Genetics of endometriosis: Current status and prospects

Family and twin studies have shown that heritability accounts for endometriosis development to an extent similar to other complex genetic diseases. Both linkage analysis and association studies have been performed to identify genetic determinants for the disease. Results from the linkage scan of 1,176 families collected thanks to a joint effort between an Australian and a UK group supported significant linkage to a novel susceptibility locus on chromosome 10q26. Although gene variants with effects on the disease predisposition have been proposed to exist and several candidates have been put forward, their effects have not been or are yet to be confirmed. The main categories of candidate genes studied have been those involved in detoxification processes, sex steroid biosynthesis and action, immune system regulation. Genetic studies on endometriosis face numerous challenges as the disease has several manifestations and different forms. Moreover, strong gene-environmental interactions might definitively influence approaches to identify genetic variants involved. Genome-wide association studies that survey most of the genome for causal genetic variants provide the potential for future progress.

Prevention of postoperative urinary stress incontinence after surgery for genitourinary prolapse

Objective To compare cystopexy alone versus cystopexy with posterior pubourethral ligaments plication for the occurrence of postoperative stress incontinence after prolapse surgery, and to compare the two surgical series in terms of complications and urodynamic effects. Methods One hundred two continent patients randomly underwent cystopexy alone (N = 52) or cystopexy with posterior pubourethral ligaments plication (N = 50). All had a urethrocystocele grade 2 or greater and a negative stress test with the prolapse repositioned. A full urodynamic investigation was repeated 6 months after surgery. Results Twelve (23%) and 14 (28%) patients (P = .73) required intermittent self-catheterization for 11.1 ± 5.1 and 16.5 ± 11.1 days, respectively (cystopexy alone versus cystopexy with posterior pubourethral ligaments plication, P = .002). Long-lasting difficulties in voiding were present in zero and five (10%) patients (P = .02). One subject receiving posterior pubourethral ligaments plication underwent urethral dilation for complete urinary retention. At 1 year follow-up, four patients (8%) in each series developed postoperative stress incontinence (P = .62). Symptomatic detrusor instability complicated the postoperative course in one patient (2%) of each group. Conclusion Cystopexy alone implied lower morbidity in terms of resumption of spontaneous voiding and long-lasting difficulties in voiding. The procedure could be recommended as an effective and safe treatment for continent patients with severe urethrocystocele. Additional plication of the posterior pubourethral ligaments did not seem superior to cystopexy alone in preventing the postoperative occurrence of stress incontinence.

Histologic analysis of specimens from laparoscopic endometrioma excision performed by different surgeons: Does the surgeon matter?

OBJECTIVE To evaluate whether the amount of ovarian tissue inadvertently removed along with the endometrioma cyst wall at laparoscopy differs in relation to the operating surgeons level of expertise. DESIGN Multicenter, prospective trial. SETTING Four tertiary care university hospitals. PATIENT(S) Fifty patients, aged 25 to 40 years, with monolateral ovarian endometriomas who underwent laparoscopic excision. INTERVENTION(S) Operation with the stripping technique by surgeons with specific expertise in endometriosis surgery in four centers (groups A, B, C, and D) and by residents with average training in laparoscopic surgery (group E). MAIN OUTCOME MEASURE(S) Histologic examination for the evaluation of the mean thickness of the cyst wall from each specimen, and the mean thickness and morphologic characteristics of any ovarian tissue removed. RESULT(S) No statistically significant differences were present in the rate of presence of ovarian tissue in the endometrioma wall specimens from the different groups (44%, 45%, 55%, 56%, and 60% in groups A, B, C, D, and E, respectively). For groups A+B+C+D versus group E, a statistically significant difference was found in the mean thickness of the tissue specimens (1.51 mm vs. 1.91 mm, respectively) and in the mean thickness of ovarian tissue inadvertently excised (0.49 mm vs. 0.97 mm, respectively). CONCLUSION(S) Level of expertise in endometriosis surgery is inversely correlated with inadvertent removal of healthy ovarian tissue along with the endometrioma capsule.

Vaginal Uterine Morcellation Within a Specimen Containment System: A Study of Bag Integrity

STUDY OBJECTIVE To evaluate the integrity of the endoscopic bag after transvaginal in-bag morcellation of uteri that need to be removed by vaginal morcellation during total laparoscopic hysterectomy (TLH). DESIGN Prospective pilot study (Canadian Task Force classification II-2). SETTING University hospital. PATIENTS Twelve patients with uteri that needed to be removed and who required vaginal morcellation underwent TLH from September 2014 to February 2015, without suspected or confirmed malignancy. INTERVENTIONS After transvaginal in-bag morcellation of uteri at the end of TLH, careful visual inspection of the endoscopic pouch, using diluted methylene blue, was carried out, highlighting any minimal bag damage. MEASUREMENTS AND MAIN RESULTS No gross rupture was encountered after morcellation; however, 4 minimal ruptures were recognized (33%) after filling up the bag with diluted methylene blue. CONCLUSIONS Minimal lesions of the bag may occur after transvaginal morcellation of uteri that need to be removed by vaginal morcellation; this may potentially affect the spread of cancer cells into the abdominal cavity.

Endocannabinoid system regulates migration of endometrial stromal cells via cannabinoid receptor 1 through the activation of PI3K and ERK1/2 pathways

OBJECTIVE To evaluate the effects of the cannabinoid system on the regulation of endometrial stromal cell (ESCs) dynamic behavior. DESIGN ESC migration, electrical signal generated by K(+) channels, and cytoskeletal-actin dynamics were evaluated in response to treatment with the synthetic endocannabinoid methanandamide. Selective agonists and antagonists were used to identify both the receptor and the biochemical pathways involved. SETTING Molecular research institution. PATIENT(S) Endometrial tissues were obtained from 40 reproductive-age women undergoing laparoscopy for benign pathologies. INTERVENTIONS ESCs were treated with methanadamide and with selective agonist (ACEA) and antagonist (AM251) of the cannabinoid receptor 1. MAIN OUTCOME MEASURES Cellular migration was evaluated by means of chemotaxis experiments in a Boyden chamber. Electric signal generated by K(+) channels was evaluated by patch clamp experiments Cellular morphology and cytoskeletal-actin dynamics were evaluated by immunofluorescence. RESULT(S) Methanandamide enhanced ESC migration via cannabinoid receptor I (CNR1) through the activation of PI3K/Akt and ERK1/2 pathways. The increased ESC migration was associated with cytoskeleton reorganization identified by the dissolution of F-actin stress fibers and the presence of stress fiber arcs and with increased electrical signal generated by K(+) channels. CONCLUSION(S) In physiologic conditions, the cannabinoid system has a central role in regulating endometrial cell migration. The involvement of ERK1/2 and PI3-K/Akt pathways points to a potential role of endocannabinoids in some pathologic conditions characterized by enhanced endometrial cell invasiveness.

Endometrial stromal cells from women with endometriosis reveal peculiar migratory behavior in response to ovarian steroids

OBJECTIVE To evaluate differences in endometrial stromal cell (ESC) migration between patients with and without endometriosis. DESIGN Differences in ESC migration, cellular morphology, and cytoskeletal-actin dynamics were evaluated in response to platelet-derived growth factor-BB (PDGF-BB) and steroid hormones (17beta-estradiol and progesterone). SETTING Medical school research laboratory. PATIENT(S) Endometrial biopsy samples obtained from 43 women: 23 as controls (endometriosis excluded by laparoscopy), 20 with severe or moderate endometriosis (diagnosed by laparoscopy). INTERVENTION(S) ESCs were treated with and without PDGF-BB, 17beta-estradiol, and progesterone. MAIN OUTCOME MEASURE(S) Cellular migration was evaluated by means of chemotaxis experiments in a Boyden chamber. Cellular morphology and cytoskeletal-actin dynamics were evaluated by immunofluorescence. RESULT(S) Progesterone stimulated the migratory behavior of ESCs derived from women with endometriosis, while 17beta-estradiol could stimulate motility of ESCs derived from both controls and women with endometriosis, with a greater effect observed in the latter group. No difference in ESC migratory behavior after PDGF-BB treatment was observed between women with and without the disease. Also, PDGF-BB and steroid hormones could modify the organization of actin cytoskeletal structures. CONCLUSION(S) Ovarian steroids differently affect the migration of ESCs derived from women with and without endometriosis. This effect is likely to involve cytoskeletal reorganization. Nongenomic signaling pathways induced by steroid hormones might have a role in this phenomenon.

Surgical excision of ovarian endometriomas: Does it truly impair ovarian reserve? Long term anti-Müllerian hormone (AMH) changes after surgery

The long‐term effects of laparoscopic cystectomy on ovarian reserve in patients with unilateral and bilateral ovarian endometriomas were evaluated.

The endocannabinoid pathway and the female reproductive organs

Endocannabinoids are endogenous ligands of cannabinoid, vanilloid and peroxisome proliferator-activated receptors that activate multiple signal transduction pathways. Together with their receptor and the enzymes responsible for their synthesis and degradation, these compounds constitute the endocannabinoid system that has been recently shown to play, in humans, an important role in modulating several central and peripheral functions including reproduction. Given the relevance of the system, drugs that are able to interfere with the activity of endocannabinoids are currently considered as candidates for the treatment of various diseases. In this review, we will summarise the current knowledge regarding the effects of endocannabinoids in female reproductive organs. In particular, we will focus on some newly reported mechanisms that can affect endometrial plasticity both in physiological and in pathological conditions.