Vittorio Palmara

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

PurposeEndometriosis 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.MethodsNarrative overview, synthesizing the findings of literature retrieved from searches of computerized databases.ResultsIn 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.ConclusionConsidering 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.

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

PurposeInvariant 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.MethodsNarrative overview, synthesizing the findings of literature retrieved from searches of computerized databases.ResultsCurrently, 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.ConclusionsAlthough 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.

Endometrial preparation with Dienogest before hysteroscopic surgery: a systematic review

PurposeHysteroscopic surgery is considered the gold standard for the minimal invasive treatment of many endouterine diseases such as endometrial polyps or submucous myomas. Recently, many studies have evaluated the effect of preoperative administration of a number of drugs to reduce endometrial thickness and achieve important intraoperative advantages. The purpose of this systematic review is to summarize the available evidence about the use of Dienogest, an orally administrable progestin, for endometrial preparation before hysteroscopic surgery.MethodsAll studies published on this topic and indexed on PubMed/MEDLINE, Embase or Google scholar databases were retrieved and analysed.ResultsWe retrieved five studies about this topic. Considered together, the published data analyses allow us to conclude that Dienogest is effective in reducing the thickness of the endometrium, the severity of bleeding and also of operative time, with a lower number of side effects compared with other pharmacological preparations or no treatment.ConclusionAdministration of Dienogest may be an effective and safe treatment for endometrial thinning before operative hysteroscopy. However, this conclusion is based on few reports and further studies to prove or disprove it are warranted.

Ectopic pregnancy in tubal remnant stump after ipsilateral adnexectomy for cystic teratoma

PurposeWe present a case of ectopic pregnancy occurring in the stump of a remnant fallopian tube following ipsilateral adnexectomy for a mature cystic teratoma.MethodsShe had a laparoscopic salpingectomy.ResultsWe hypothesize the intrauterine transmigration of the fecundated ovum.ConclusionsThe authors emphasize the rarity of the observed case.

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

Abstract 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.

Robotic surgery and standard laparoscopy: A surgical hybrid technique for use in colorectal endometriosis

Aim:  The aim of our work was to assess the feasibility and possible benefits of a novel hybrid surgical technique in rectosigmoidal resection in patients with bowel endometriosis.

Fasting as possible complementary approach for polycystic ovary syndrome: hope or hype?

Polycystic ovary syndrome (PCOS) is a common endocrine system disorder among women of reproductive age. In several cases, PCOS women show infertility or subfertility and other metabolic alteration, such as insulin resistance (InsR), dyslipidaemia, hyperinsulinemia and obesity. Despite the aetiology of the syndrome is still far from be elucidated, it could be considered the result of concurrent endocrine modifications, lifestyle factors and genetic background. In particular, accumulating evidence suggests that InsR and compensatory hyperinsulinemia play a pivotal pathogenic role in the hyperandrogenism of many PCOS phenotypes, which in turn have a clear detrimental effect on chronic anovulation. Different forms of fasting, such as intermittent fasting (IF, including alternate day fasting, or twice weekly fasting, for example) and periodic fasting (PF, lasting several days or longer every 2 or more weeks) are currently being tested in several in vitro and in vivo studies. Changes in the circulating levels of Insulin Growth Factor-1 (IGF-1), Insulin-like Growth Factor-Binding Protein 1 (IGFBP1), glucose and insulin are typical effects of fasting which may play a key role on aging and metabolic homeostasis. Considering the paramount importance of InsR and compensatory hyperinsulinemia, different fasting regimens can reduce IGF-1, IGFBP1, glucose and insulin levels and consequently have beneficial effects on ovarian function, androgen excess and infertility in PCOS women.

Do miRNAs Play a Role in Fetal Growth Restriction? A Fresh Look to a Busy Corner

Placenta is the crucial organ for embryo and fetus development and plays a critical role in the development of fetal growth restriction (FGR). There are increasing evidences on the role of microRNAs (miRNAs) in a variety of pregnancy-related complications such as preeclampsia and FGR. More than 1880 miRNAs have been reported in humans and most of them are expressed in placenta. In this paper, we aimed to review the current evidence about the topic. According to retrieved data, controversial results about placental expression of miRNAs could be due (at least in part) to the different experimental methods used by different groups. Despite the fact that several authors have demonstrated a relatively easy and feasible detection of some miRNAs in maternal whole peripheral blood, costs of these tests should be reduced in order to increase cohorts and have stronger evidence. In this regard, we take the opportunity to solicit future studies on large cohort and adequate statistical power, in order to identify a panel of biomarkers on maternal peripheral blood for early diagnosis of FGR.

Levonorgestrel-releasing intrauterine device in the treatment of abnormal uterine bleeding: a 6- and 12-month morphological and clinical follow-up.

Abnormal uterine bleeding is defined as any alteration in the pattern or volume of menstrual blood flow, and it is preferably treated using hysterectomy, endometrial destruction or the levonorgestrel‐releasing intrauterine system (Mirena®). Recently, it has been demonstrated that studies of Mirena® were generally small and consequently imprecise.