Compensatory Feto-Placental Upregulation of the Nitric Oxide System during Fetal Growth Restriction

Background: Fetal Growth Restriction is often associated with a feto-placental vascular dysfunction conceivably involving endothelial cells. Our study aimed to verify this pathogenic role for feto-placental endothelial cells and, coincidentally, demonstrate any abnormality in the nitric oxide system. Methods: Prenatal assessment of feto-placental vascular function was combined with measurement of nitric oxide (in the form of S-nitrosohemoglobin) and its nitrite byproduct, and of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine. Umbilical vein endothelial cells were also harvested to determine their gene profile. The study comprised term pregnancies with normal (n = 40) or small-for-gestational-age (n = 20) newborns, small-for-gestational-age preterm pregnancies (n = 15), and bi-chorial, bi-amniotic twin pregnancies with discordant fetal growth (n = 12). Results: Umbilical blood nitrite (p<0.001) and S-nitrosohemoglobin (p = 0.02) rose with fetal growth restriction while asymmetric dimethylarginine decreased (p = 0.003). Nitrite rise coincided with an abnormal Doppler profile from umbilical arteries. Fetal growth restriction umbilical vein endothelial cells produced more nitrite and also exhibited reciprocal changes in vasodilator (upwards) and vasoconstrictor (downwards) transcripts. Elevation in blood nitrite and S-nitrosohemoglobin persisted postnatally in the fetal growth restriction offspring. Conclusion: Fetal growth restriction is typified by increased nitric oxide production during pregnancy and after birth. This response is viewed as an adaptative event to sustain placental blood flow. However, its occurrence may modify the endothelial phenotype and may ultimately represent an element of risk for cardiovascular disease in adult life.Fil: Pisaneschi, Silvia. Università degli Studi di Pisa; Italia. Scuola Superiore Sant’Anna; ItaliaFil: Strigini, Francesca A. L.. Università degli Studi di Pisa; ItaliaFil: Sanchez, Angel Matias. Università degli Studi di Pisa; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Begliuomini, Silvia. Università degli Studi di Pisa; ItaliaFil: Casarosa, Elena. Università degli Studi di Pisa; ItaliaFil: Ripoli, Andrea. National Research Council. Institute of Clinical Physiology, ; ItaliaFil: Ghirri, Paolo. Università degli Studi di Pisa; ItaliaFil: Boldrini, Antonio. Università degli Studi di Pisa; ItaliaFil: Fink, Bruno. Noxygen Science Transfer and Diagnostics; AlemaniaFil: Genazzani, Andrea R.. Università degli Studi di Pisa; ItaliaFil: Coceani, Flavio. Scuola Superiore Sant’Anna; ItaliaFil: Simoncini, Tommaso. Università degli Studi di Pisa; Itali

Robotic Approach to Ureteral Endometriosis: Surgical Features and Perioperative Outcomes

Introduction: Surgical treatment of ureteral endometriosis is necessary to relieve urinary symptoms of obstruction and to preserve renal function. Which surgical approach to ureteral endometriosis should be considered the most appropriate is debated, due to the lack of scientific evidence. The aim of the present study is to assess the feasibility and to describe the perioperative outcomes of minimally invasive treatment of deep ureteral endometriosis using robotic assistance, highlighting the technical benefits and the limits of this approach. Method: A case-series including 31 consecutive patients affected by high-stage endometriosis including ureteral endometriosis using robotic assistance in our Department between November 2011 and September 2017. Results: All procedures were successfully completed by robotic technique, resulting in full excision of the parametrial nodules involving the ureter. Mean operating time was 184.8 ± 81min. Mean hospital stay was 4.02 ± 3 days. Perioperative complications occurred in five patients and 4 out of 5 involved the urinary tract. Conclusions: Robotic surgery for deep infiltrating endometriosis of the ureter was feasible and allowed complete resection of ureteral nodules in all cases. No intraoperative complications arose, but a non-negligible rate of urinary tract complications was detected. This calls for a careful assessment of the benefits and specific risks associated with the use of robotic surgery for the treatment of deep infiltrating endometriosis of the ureter

Overactive feto-placental nitric oxide system during pre- and perinatal insult

Background Endothelium-derived nitric oxide (NO) is a highly reactive inorganic free radical with widespread biological actions, including vascular regulation, neurotransmission, hormone secretion and inflammation. Potential roles for NO in the human uterus include vasodilatation (both before implantation, and in the uteroplacental and systemic circulation during pregnancy). Nitric oxide may also be involved in diseases of pregnancy, from unexplained infertility and recurrent miscarriage and/or defective placentation in the first period of gestation. During the third trimester of pregnancy, a change in the NO production may be involved in pre-eclampsia and fetal growth restriction (FGR). NO may also have a compensatory function, and several situations in the adult document this possibility. This thesis aimed to verify whether the NO activation represents a unifying mechanism for the preservation of blood delivery to the fetus during different adverse conditions. The working hypothesis was that endothelial cells from feto-placental vessels are key determinants of any situation in which the fetus is exposed to a hypoxic insult and requires an adequate amount of oxygen for well-being, including chronic hypoxemia leading to FGR and transitory hypoxiemia during normal or disturbed labor. Further we aimed to define the nature of any linkage between NO and FGR and, coincidentally, provide a possible insight into the alleged negative impact of FGR on adult health. Methods The approach was comprehensive and included: (i) measurement of NO and its main metabolite, nitrite (NO2), along with the natural NO synthase inhibitor asymmetric dimethylarginine (ADMA); (ii) analysis of Doppler velocimetry in umbilical arteries; and (iii) assessment of gene profile in umbilical vein endothelial cells (HUVEC) collected at the time of delivery. Study comprised term pregnancies with average (n =40) or small-for-gestational age body weight (n = 20) (both scheduled for umbilical Doppler velocimetry at 36 wk), pregnancies with isolated preterm FGR (n = 15) and bi-chorial, bi-amniotic twin pregnancies with discordant fetal growth (n = 12). Cord blood (artery and vein) was collected in all cases, while peripheral blood (heel sampling) was obtained from certain newborns at the time of delivery and 24 or 72 h afterwards. A second analysis was performed on the sub-group of pregnancies where delivery of a normal newborn had occurred at term, either vaginally or through cesarean section without/with prior labor (n = 20). In addition, cases from the same cohort but not considered earlier, where delivery had been complicated by fetal hypoxia (n = 15), were examined. Then, collective values were cross-analyzed depending on the mode of delivery and the presence/absence of fetal hypoxia. Separately, the same variables were measured over the first three days of life in term neonates from vaginal and cesarean (with/without labor) delivery uncomplicated by hypoxia. Results The NO system within the placenta and the fetus itself may be important in maintaining a suitable oxygenation of the offspring through any intervening hypoxic insult. Compensatory feto-placental up-regulation of the NO system during FGR was shown. In detail, umbilical blood nitrite (p < 0.001) and S-nitrosohemoglobin (p = 0.02) rose with fetal growth restriction while asymmetric dimethylarginine decreased (p = 0.003). Nitrite rise coincided with an abnormal Doppler profile from umbilical arteries. Our analysis of the expression of a wide set of endothelial genes suggests that this phenomenon is part of a re-setting of endothelial function, as an adaptative event to sustain placental blood flow. In fact, in the presence of fetal growth restriction, umbilical vein endothelial cells produced more nitrite and also exhibited reciprocal changes in vasodilator (upwards) and vasoconstrictor (downwards) transcripts. Moreover, elevation in blood nitrite and S-nitrosohemoglobin persisted post-natally in the fetal growth restriction offspring, potentially modifying the endothelial phenotype and possibly representing an element of risk for cardiovascular disease in adult life. Similarly to FGR, where NO may be of use to counteract chronic impairment in oxygen inflow to the fetus, fetal and placental NO may also be important to facilitate blood flow to the fetus during labor and delivery. In particular, active labor was associated with higher NO and NOHb concentrations in the umbilical vein blood. Accordingly, HUVEC from labor-based deliveries presented greater eNOS expression and activity. The same blood variables, however, presented an opposite trend in the umbilical artery. Further activation of the NO system occurred with deliveries complicated by offspring hypoxia along with a fall of ADMA levels. This set of responses may help adapt to post-natal breathing, extending the potential protective role of NO to the peri-partum period; in fact, the upward change in NO activity progressed over the first 24 hrs after birth to subside by 72 hrs. Conclusions The role of NO in diverse uterine conditions may have great clinical implications in developing therapeutic strategies to prevent NO-related disorders. Indeed, if a role for NO is confirmed, pharmacological modification of NO activity may lead to novel therapeutic applications. Moreover, the NO system within the placenta and the fetus itself may be important in maintaining a suitable oxygenation of the offspring through any intervening hypoxic insult. FGR is typified by increased nitric oxide production during pregnancy and after birth. This response is viewed as an adaptive event to sustain placental blood flow. However, the phenotypic characteristics of endothelial cells linked to the synthesis of NO might contribute some sort of imprinting to the vulnerable newborn determining functional vascular changes that may be important for postnatal adaptation but that may as well be long-lasting, possibly programming the infant in the long-term. As the NO system is a key player in preserving fetal oxygen availability in chronic conditions of increased demand, transitory hypoxemia during delivery is associated with enhanced NO function in the feto-placental district with a concomitant greater utilization of the agent by the fetus. This normal event is magnified with intra-partum hypoxia and, in all cases, persists in the immediate post-natal period. We regard this set of changes as a protective mechanism whose finality is to maintain an adequate oxygenation of the fetus through delivery with an attendant smooth transition from intra- to extra-uterine life

APPROCCIO ROBOTICO ALL' ENDOMETRIOSI URETERALE: IMPLICAZIONI CHIRURGICHE E OUTCOMES PERIOPERATORI

Il trattamento chirurgico dell’endometriosi ureterale è necessario nella paziente che presenta sintomi urinari di ostruzione e per preservare la funzione renale. Quale approccio chirurgico per il trattamento dell’endometriosi ureterale sia il più appropriato rimane ad oggi dibattuto per l’assenza di evidenze scientifiche. L’obbiettivo di questo studio è la valutazione della fattibilità del trattamento mininvasivo dell’endometriosi profondamente infiltrante usando la chirurgia robotica, descrivere gli outcames perioperatori, evidenziare i benefici della tecnica e i limiti di questo approccio. Questo studio include 21 pazienti affette da endometriosi in stadio avanzato con interessamento ureterale che sono state sottoposte a chirurgia robot-assistita nel nostro dipartimento tra Novembre 2011 e Settembre 2017. Tutte le procedure chirurgiche sono state completate con tecnica robot-assistita, raggiungendo l’escissione completa del nodulo parametriale che coinvolgeva l’uretere. Il tempo operatorio medio è stato 184.8 ± 81 min. il tempo di ospedalizzazione medio è stato di 4.02 ± 3 giorni. Le complicanze perioperatorie si sono verificate in 5 pazienti e in 4 su 5 coinvolgevano il tratto urinario. Possiamo concludere che la chirurgia robotica è fattibile in caso di endometriosi profondamente infiltrante con interessamento dell’uretere e ha permesso una completa resezione del nodulo in tutti i casi. Non si sono verificate numerose complicanze intraoperatorie, ma un tasso non trascurabile ha coinvolto il tratto urinario. Resta quindi necessaria un’attenta valutazione dei benefici e dei rischi specifici associati con l’uso della chirurgia robotica per il trattamento dell’endometriosi profondamente infiltrate dell’uretere

Menopause, Aging, Pelvic Organ Prolapse, and Dysfunction

The female pelvic floor is a complex functional unit involved in many undertakings. Pelvic floor dysfunction affects micturition, defecation, and sexual activity. Evolutionary adaptation, such as the acquisition of the upright standing position, walking, and delivery of fetuses with larger head diameters, made the fascial and the muscle support of the pelvic floor more vulnerable, predisposing women to pelvic organ prolapse and incontinence. In addition, the female pelvic floor (differently than in males) undergoes a number of adaptive changes related to life and endocrine events. Many of these clinical manifestations become apparent after menopause and aging in women. This chapter summarizes the key aspects of the pathophysiology and the clinics of the changes of the pelvic floor in women, in particular focusing on the association between endocrine changes of aging women and urinary problems and bowel dysfunctions.Fil: Pisaneschi, Silvia. Universitá di Pisa; ItaliaFil: Palla, Giulia. Universitá di Pisa; ItaliaFil: Spina, Stefania. Universitá di Pisa; ItaliaFil: Bernacchi, Guja. Universitá di Pisa; ItaliaFil: Cecchi, Elena. Universitá di Pisa; ItaliaFil: Di Bello, Silvia. Universitá di Pisa; ItaliaFil: Montt Guevara, Maria Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universitá di Pisa; ItaliaFil: Campelo, Adrián Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina. Università di Pisa; ItaliaFil: Simoncini, Tommaso. Universitá di Pisa; Itali

First series of total robotic hysterectomy (TRH) using new integrated table motion for the da Vinci Xi: feasibility, safety and efficacy

BACKGROUND: To present the first case series of total robotic hysterectomy (TRH), using integrated table motion (ITM), which is a new feature comprising a unique operating table by Trumpf Medical that communicates wirelessly with the da Vinci Xi surgical system. ITM has been specifically developed to improve multiquadrant robotic surgery such as that conducted in colorectal surgery. METHODS: Between May and October 2015, a prospective post-market study was conducted on ITM in the EU in 40 cases from different specialties. The gynecological study group comprised 12 patients. Primary endpoints were ITM feasibility, safety and efficacy. RESULTS: Ten patients underwent TRH. Mean number of ITM moves was three during TRH; there were 31 instances of table moves in the ten procedures. Twenty-eight of 31 ITM moves were made to gain internal exposure. The endoscope remained inserted during 29 of the 31 table movements (94%), while the instruments remained inserted during 27 of the 31 moves (87%). No external instrument collisions or other problems related to the operating table were noted. There were no ITM safety-related observations and no adverse events. CONCLUSIONS: This preliminary study demonstrated the feasibility, safety and efficacy of ITM for the da Vinci Xi surgical system in TRH. ITM was safe, with no adverse events related to its use. Further studies will be useful to define the real role and potential benefit of ITM in gynecological surgery.