Regulation of apoptotic pathways during endometriosis: from the molecular basis to the future perspectives.

PURPOSE: Endometriosis is defined as the presence of endometrial-like endometrial cells, glands and stroma outside the uterus, causing a strong inflammatory-like microenvironment in the affected tissue. This may provoke a breakdown in the peritoneal cavity homeostasis, with the consequent processes of immune alteration, documented by peripheral mononuclear cells recruitment and secretion of inflammatory cytokines in early phases and of angiogenic and fibrogenic cytokines in the late stages of the disease. Considering the pivotal role of interaction between immune and endometriotic cells, in this paper, we aim to shed light about the role of apoptosis pathways in modulating the fine-regulated peritoneal microenvironment during endometriosis. METHODS: Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases. RESULTS: In normal conditions, endometriotic cells, refluxed through the fallopian tubes into the peritoneal cavity, should be attacked and removed by phagocytes and NK cells. During endometriosis, the breakdown of peritoneal homeostasis causes the failure of scavenging mechanisms, allowing the survival of endometriotic cells. The consequent so-called "immunoescaping" of endometriotic cells could be due, at least in part, to the reduction of apoptotic-mediated pathways previously described. CONCLUSION: Considering the large amount of evidence retrieved from in vitro as well as in vivo models, the reduced apoptosis of endometriotic cells together with the increased apoptosis of peritoneal fluid mononuclear cells may address the peritoneal homeostasis to a permissive environment for the progression of the disease.

Full-Thickness Excision versus Shaving by Laparoscopy for Intestinal Deep Infiltrating Endometriosis: Rationale and Potential Treatment Options.

Endometriosis is defined as the presence of endometrial mucosa (glands and stroma) abnormally implanted in locations other than the uterine cavity. Deep infiltrating endometriosis (DIE) is considered the most aggressive presentation of the disease, penetrating more than 5 mm in affected tissues, and it is reported in approximately 20% of all women with endometriosis. DIE can cause a complete distortion of the pelvic anatomy and it mainly involves uterosacral ligaments, bladder, rectovaginal septum, rectum, and rectosigmoid colon. This review describes the state of the art in laparoscopic approach for DIE with a special interest in intestinal involvement, according to recent literature findings. Our attention has been focused particularly on full-thickness excision versus shaving technique in deep endometriosis intestinal involvement. Particularly, the aim of this paper is clarifying from the clinical and methodological points of view the best surgical treatment of deep intestinal endometriosis, since there is no standard of care in the literature and in different surgical settings. Indeed, this review tries to suggest when it is advisable to manage the full-thickness excision or the shaving technique, also analyzing perioperative management, main complications, and surgical outcomes.

Oxidative Stress during Ovarian Torsion in Pediatric and Adolescent Patients: Changing The Perspective of The Disease.

Among the different causes of gynecological acute pelvic pain, ovarian torsion represents a surgical emergency. It is a rare case in the pediatric/adolescent aged group that must be included in the differential diagnosis of any girl with abdominal pain or pelvic/abdominal mass. Current recommendations suggest that laparoscopic detorsion should be performed in order to preserve the integrity of the ovaries and fertility, although oophoropexy may be considered in case of severe necrosis. Nevertheless, maintaining the circulation of the ovary after detorsion deteriorates the tissue injury and leads to a pathologic process called ischaemia/reperfusion (I/R) injury, which is characterized by oxidative stress. During the detorsion process, an excess amount of molecular oxygen is supplied to the tissues, and reactive species of oxygen (ROS) such as superoxide radical (O2 (-)), hydrogen peroxide (H2O2), hydroxyl radical (OH•), as well as reactive nitrogen species (RNS) are produced in excess. ROS, RNS and their toxic products cause DNA damage and lipid peroxidation in the cellular and mitochondrial membranes, leading to cell death. In spite of attention on this topic, currently there is no shared and clear evidence about the use of anti-inflammatory and antioxidant agents to prevent I/R damage after laparoscopic ovarian detorsion. Considering this element, future research should aim to develop shared protocols for the clinical use (route of application, dosage and time of application) of antioxidants after laparoscopic management of this condition.

Natural Killer T cell subsets in eutopic and ectopic endometrium: a fresh look to a busy corner.

PURPOSE: Invariant Natural Killer T cells (iNKT) are a specialized subset of T cells that use their T cell receptor to recognize self and foreign lipids presented by CD1d as cognate antigens. iNKT have been shown to have either protective or harmful roles in many pathological states, including microbial infection, autoimmune disease, allergic disease and cancer. Accumulating evidence seems to suggest that this unique T cell subset combines both classically innate and adaptive immunologic characteristic. Considering these recent data, the aim of work was to review the current knowledge about iNKT in eutopic and ectopic endometrium. METHODS: Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases. RESULTS: Currently, the immune paradigm of reproduction is gradually changing shape: recent data confirmed that cytokine milieu influences the development and plasticity of different subtype of mononuclear cells, and in turn it can be influenced by the cytokine production of the latter. Among the different NKT cell populations, the recently characterized iNKT seems to share actions typical both of innate and adaptive immunity, being capable of secreting Th1 as well as Th2 cytokine pattern. Moreover, several subtypes of iNKT were identified, who partially express the same master transcription factors of the corresponding T cells counterpart. CONCLUSIONS: Although the data about iNKT's actions in eutopic and ectopic endometrium are still scarce, it is possible to hypothesize that future investigation can shed light on this point, thus allowing a better knowledge about the regulation of these two microenvironments.

Dienogest as preoperative treatment of submucous myomas for hysteroscopic surgery: a prospective, randomized study.

The aim of this single-center, prospective, randomized, parallel-group study was to compare Dienogest and Danazol as endometrial preparation in patients who have to undergo hysteroscopic surgery for submucous myomas. We enrolled 80 consecutive eligible patients, in reproductive age, affected by submucous myomas. Pre- and posttreatment characterization of endometrium was performed by hysteroscopic visual observation and histologic confirmation. The enrolled patients were randomly assigned to two groups: 40 were treated with 2 mg of Dienogest/die, 40 with 100 mg of Danazol/die, both orally for 5 weeks, starting on day 1 of menstruation. Posttreatment comparison of endometrial patterns showed a significant more marked effect of Dienogest, respect to Danazol, in atrophying endometrium ("normotrophic non-responders" versus "hypotrophic"-"atrophic", p = 0.028). Intraoperative data showed no significant difference between the two groups for cervical dilatation time (p = 0.326), while in the Dienogest group, we found a significant reduction of operative time (p = 0.001), infusion volume (p = 0.001), and severity of bleeding (p = 0.042). Moreover, Dienogest caused less side effects (p = 0.008). According to our data analysis, Dienogest, respect to Danazol, is more effective for the preparation of the endometrium in patients who have to undergo hysteroscopic surgery for submucous myomas, and causes less side effects.

Does epidural analgesia play a role in postpartum urinary incontinence? Medium-term results from a case-control study.

OBJECTIVE: To evaluate the medium-term effect of epidural analgesia (EA) on the possible onset of postpartum urinary incontinence (PUI). METHODS: We performed a single-centre, retrospective case-control study. At 8-week postpartum, we recruited a cohort of women who had term singleton pregnancy and foetus in cephalic presentation, and divided in six groups: (1) vaginal delivery without episiotomy, without EA; (2) vaginal delivery without episiotomy, with EA; (3) vaginal delivery with episiotomy, without EA; (4) vaginal delivery with episiotomy, with EA; (5) emergency caesarean section without previous EA during labour and (6) emergency caesarean section with previous EA during labour. For each woman, we recorded age, Body Mass Index (BMI) and the result of the following questionnaire for urinary incontinence: International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), Incontinence Impact Questionnaire-7 (IIQ-7) and Urogenital Distress Inventory-6 (UDI-6). Subsequently, we compared group 1 versus group 2, group 3 versus group 4 and group 5 versus group 6. RESULTS: We did not evidence any significant difference for age, BMI and incontinence scores between groups 1 and 2, 3 and 4, and 5 and 6. CONCLUSIONS: EA did not affect the onset of PUI in medium-term, regardless the mode of delivery.