New technologies in the surgical management of endometriosis

Introduction: Endometriosis is a very common disease that affects up to 10% of the female population. Although medical therapy represents the first-line treatment for endometriosis, it does not always manage to control symptoms. Laparoscopy represents the standard surgical treatment in endometriosis. Robotic-assisted laparoscopy is an innovative mini-invasive surgical technique. Its application in gynecological surgery and in endometriosis has increased in the last decade. Our purpose is to offer an overview of the role of robotic-assisted laparoscopy in the surgical treatment of endometriosis. Methods: We evaluated studies dealing with the new technique in surgery for endometriosis with a focus on robotic surgery. We performed a compressive literature research on PubMed and the Cochrane Library in December 2022. Expert opinion: Robotic-assisted surgery is a feasible and safe approach to endometriosis surgery and is superimposable to laparoscopy in terms of complication rate, blood loss, hospitalization, and long-term improvement of symptoms. The effect of robotic-assisted surgery on operative time is still contradictory and needs to be further investigated. Robotic-assisted laparoscopic surgery can provide particular benefit in the management of women with severe endometriosis secondary to its advantage in surgical precision and ergonomics. Indocyanine green fluorescence angiography could be useful to assist in the vascularization of ureters and bowel anastomosis, to prevent postoperative complication and leakage

Hysterectomy by transvaginal natural orifice transluminal endoscopic surgery: An Italian initial experience

BackgroundThe aim of this study is to evaluate the initial feasibility, safety, and outcomes of hysterectomy performed by transvaginal natural orifice transluminal endoscopic surgery (vNOTES) at three institutions in Italy.Materials and methodsAll women who underwent vNOTES hysterectomy ± salpingo-oophorectomy for benign indications at three tertiary referral medical centers between July 2019 and April 2021 were included in a retrospective analysis. All vNOTESs were performed with the use of Alexis® and Vpath Gel paths® (Applied Medical). Perioperative data were extracted from patient records. Patient satisfaction and dyspareunia were prospectively inquired about at 60 days and 6 months.ResultsForty-six patients underwent vNOTES in the study period. Indications for surgery included myomas ± metrorrhagia (52.2%), H-Sil/in situ cervical cancer (10.7%), adenomyosis ± metrorrhagia (8.7%), BRCA 1-2 mutations (6.5%), endometrial hyperplasia (6.5%), ovarian cyst + history of breast cancer (6.5%), metrorrhagia (6.5%), and hydatidiform mole (2.2%). The mean operation time was 91.1 (±32.6) minutes. The mean hemoglobin drop was 1.2 (±0.8). The mean visual analog scale at 24 h for post-operative pain was 3.3 (±1.8). Secondary to our limited experience with the surgical technique, we favor discharge only from day 1. The mean length of hospital stay was 2 (±1.4) days. Two conversions to conventional laparoscopy were reported (4.3%), due to an obliterated pouch of Douglas and a preoperative complication. Two post-operative complications were reported (4.3%). Overall, our data on peri- and post-operative outcomes are similar to those already published for vNOTES.ConclusionOur initial experience suggests that introducing vNOTES as an alternative to conventional surgery is feasible and may offer some advantages in selected women

Robotic-assisted vs conventional laparoscopic management of deep endometriosis involving sacral plexus and sciatic nerve: a comparative before and after study

Background: Endometriosis is characterized by the presence of endometrial-like gland and stroma outside of the uterine cavity. It causes chronic inflammation, fibrosis, anatomic distortion and adhesion formation. Deep infiltrating endometriosis involving sacral plexus and sciatic nerve is a rare localization. Depending by the degree of nerve involvement, the disease can produce severe symptoms as sciatic or pudendal pain and refractory urinary, anorectal and sexual dysfunction. The aim of the present study is to compare robotic-assisted laparoscopy and conventional laparoscopic for intraoperative, postoperative and functional outcomes among patients undergoing excision of deep infiltrating endometriosis involving sacral plexus and sciatic nerve. Materials and methods: We performed a retrospective analysis of patients referred to the Institut Franco-Européen Multidisciplinaire d'Endométriose (IFEMEndo), Clinique Tivoli-Ducos, Bordeaux, for deep infiltrating endometriosis involving sacral roots and/or sciatic nerve between September 2018 and June 2023. Patients underwent to surgery for endometriosis eradication by conventional laparoscopic (LPS, n=71) until 2021. After the introduction in our practice of Da Vinci Surgical System X (Intuitive Surgical Inc., Sunnyvale, CA, U.S.), the patients were systematically managed by robotic-assisted laparoscopy (RAL, n=29). In both the surgical approach, the excision of deep infiltrating endometriosis involving sacral plexus and sciatic nerve followed the same standardized surgical procedures. We compared intraoperative, perioperative data and functional outcome after 6 month follow up. Results: A total of 100 patients met the inclusion criteria for our study. Seventy-one consecutive patients were managed in LPS group, and 29 consecutive patients underwent to RAL group. The two groups were comparable in terms of basal complain and distribution of deep infiltrating endometriosis lesions. Nerve dissection, nerve shaving and intra-nerve dissection were performed respectively in 77.5%, 19.7% and 5.6% of patients in the LPS group, and 82.8%, 17.2% and 6.9% in the RAL group (p=0.43). Mean operative time was respectively 183.785.3 min and 177.477.2 min (p=0.73). In no case we experienced conversion to open surgery. We did not observe a statistically significant difference in intra- operative and early post-operative complication between the two groups. After 6 month follow up, we observed significant reduction of the rate of sciatic pain in both LPS group (39.1 vs 15.6, p<0.0001) and RAL group (37.5 vs 25, p=0.001), without any statistically significant differences in terms of outcomes (p=0.1). The 33.8% of LPS group and the 34.5% of patients of RAL group required self-catheterization after surgery. Digestive function, measured through the Gastrointestinal Quality of Life index (GIQLI) showed a significant improvement in overall gastrointestinal global well-being in both groups. After 6 month follow up, digestive and urinary outcomes outcomes result to be superimposable in the two group (p=ns). After 1 year follow up 5.6% of patient in LPS group still required self-catheterization, meanwhile no patients in the RAL group still required self-catheterization after 1 year (p=0.44). Conclusion: Conventional and robotic-assisted laparoscopy are feasible and effective approach for the surgical management of DIE involving sacral plexus and sciatic nerve. Both the techniques result in a significant long-term relief of symptoms related to sacral plexus and sciatic nerve endometriosis. Although surgeons found that the robotic assistance improved the quality of the excision of these specific localizations of the disease, our study did not reveal statistically significant advantages in terms of outcomes

Music Modulates Autonomic Nervous System Activity in Human Fetuses

CONTEXT: Fetal Autonomic Nervous sysTem Evaluation (FANTE) is a non-invasive tool that evaluates the autonomic nervous system activity in a fetus. Autonomic nervous system maturation and development during prenatal life are pivotal for the survival and neuropsychiatric development of the baby. OBJECTIVE: Aim of the study is to evaluate the effect of music stimulation on fetal heart rate and specific parameters linked to ANS activity, in particular fetal heart rate variability. METHODS: Thirty-two women between the 32nd and 38th week with a singleton uncomplicated pregnancy were recruited. All FANTE data collections were acquired using a 10-derivation electrocardiograph placed on the maternal abdomen. In each session (5 min basal, 10 min with music stimulus, and 5 min post-stimulus), FANTE was registered. The music stimulus was “Clair de lune” Debussy, played through headphones on the mother’s abdomen (CTR: 31927). RESULTS: Music does not change the mean value of fetal heart rate. However, indices of total fetal heart rate variability statistically increase (RRsd p = 0.037, ANNsd p = 0.039, SD2 p = 0.019) during music stimulation in comparison to the basal phase. Heart rate variability increase depends mainly on the activation of parasympathetic branches (CVI p = 0.013), meanwhile, no significant changes from basal to stimulation phase were observed for indices of sympathetic activity. All the parameters of heart rate variability and parasympathetic activity remained activated in the post-stimulus phase compared to the stimulus phase. In the post-stimulus phase, sympathetic activity resulted in a significant reduction (LFn p = 0.037). CONCLUSION: Music can influence the basal activity of the fetal autonomic nervous system, enhancing heart rate variability, without changing fetal heart rate mean value. Music is enabled to induce a relaxation state in a near-to-term fetus, mediated by parasympathetic activation and by a parallel sympathetic inhibition

De novo missense variants in phosphatidylinositol kinase PIP5KIγ underlie a neurodevelopmental syndrome associated with altered phosphoinositide signaling

Phosphoinositides (PIs) are membrane phospholipids produced through the local activity of PI kinases and phosphatases that selectively add or remove phosphate groups from the inositol head group. PIs control membrane composition and play key roles in many cellular processes including actin dynamics, endosomal trafficking, autophagy, and nuclear functions. Mutations in phosphatidylinositol 4,5 bisphosphate [PI(4,5)P2] phosphatases cause a broad spectrum of neurodevelopmental disorders such as Lowe and Joubert syndromes and congenital muscular dystrophy with cataracts and intellectual disability, which are thus associated with increased levels of PI(4,5)P2. Here, we describe a neurodevelopmental disorder associated with an increase in the production of PI(4,5)P2 and with PI-signaling dysfunction. We identified three de novo heterozygous missense variants in PIP5K1C, which encodes an isoform of the phosphatidylinositol 4-phosphate 5-kinase (PIP5KIγ), in nine unrelated children exhibiting intellectual disability, developmental delay, acquired microcephaly, seizures, visual abnormalities, and dysmorphic features. We provide evidence that the PIP5K1C variants result in an increase of the endosomal PI(4,5)P2 pool, giving rise to ectopic recruitment of filamentous actin at early endosomes (EEs) that in turn causes dysfunction in EE trafficking. In addition, we generated an in vivo zebrafish model that recapitulates the disorder we describe with developmental defects affecting the forebrain, including the eyes, as well as craniofacial abnormalities, further demonstrating the pathogenic effect of the PIP5K1C variants. We describe a neurodevelopmental disorder associated with de novo gain-of-function variants in PIP5KIγ kinase. The variants cause perturbed endosomal function resulting from increased production of phosphatidylinositol 4,5 bisphosphate and enhanced association of F-actin at endosomes. Moreover, mutant zebrafish larvae recapitulate the phenotypes observed in affected individuals from our cohort