Daniela Surico

Differential expression of microRNAs between eutopic and ectopic endometrium in ovarian endometriosis.

Endometriosis, defined as the presence of endometrial tissue outside the uterus, is a common gynecological disease with poorly understood pathogenesis. MicroRNAs are members of a class of small noncoding RNA molecules that have a critical role in posttranscriptional regulation of gene expression by repression of target mRNAs translation. We assessed differentially expressed microRNAs in ectopic endometrium compared with eutopic endometrium in 3 patients through microarray analysis. We identified 50 microRNAs differentially expressed and the differential expression of five microRNAs was validated by real-time RT-PCR in other 13 patients. We identified in silico their predicted targets, several of which match the genes that have been identified to be differentially expressed in ectopic versus eutopic endometrium in studies of gene expression. A functional analysis of the predicted targets indicates that several of these are involved in molecular pathways implicated in endometriosis, thus strengthening the hypothesis of the role of microRNAs in this pathology.

A multicentric trial (Olympia–MITO 13) on the accuracy of laparoscopy to assess peritoneal spread in ovarian cancer

OBJECTIVE The objective of the study was to prospectively evaluate the accuracy of laparoscopy performed in satellite centers (SCs) to describe intraabdominal diffusion of advanced ovarian cancer (AOC). STUDY DESIGN Patients with a clinical/radiological suspicion of AOC were included in the protocol. SCs were selected among those surgeons, spending a short intensive training period at the coordinator center (CC) to learn the application of staging laparoscopy (S-LPS) in AOC. All women underwent S-LPS at the SCs, and the surgical procedure was recorded and blindly reviewed at the CC. Calculating specificity, positive and negative predictive values, and the accuracy for each parameter with respect to the CC assessed the diagnostic performance of S-LPS. The Cohens kappa was used to test the interobserver agreement of each parameter. RESULTS One hundred sixty-eight cases were considered eligible for the study. A per-protocol analysis was performed on 120 cases. The worst laparoscopic assessable feature was mesenteric retraction, whereas the remaining variables ranged from 99.2% (peritoneal carcinomatosis) to 90% (bowel infiltration). All but 1 SC (SC number 4) reached an accuracy rate of 80% or greater for both single parameters and overall score. The Cohens kappa and the P value for overall predicitive index value were 0.685 and .01, respectively, but improved to 0.773 and .388 after removing the SC number 4 from the analysis. CONCLUSION S-LPS allows an accurate and reliable assessment of intraperitoneal diffusion of disease in AOC patients in trained gynecological oncology centers.

Laparoscopy versus minilaparotomy in women with symptomatic uterine myomas: short-term and fertility results

OBJECTIVE To retrospectively compare the feasibility, safety, morbidity, and pregnancy outcome of laparoscopy (LPS) and minilaparotomy (LPT) in the treatment of symptomatic uterine myomas. DESIGN Retrospective, nonrandomized study. SETTING Advanced Gynecological Endoscopy Center, Malzoni Medical Center, Avellino, Italy. PATIENT(S) 680 nonconsecutive patients with symptomatic uterine myomas. INTERVENTION(S) 350 women underwent LPS, and 330 underwent LPT myomectomy. MAIN OUTCOME MEASURE(S) Operative time, blood loss, hospital stay, pregnancy rate, and spontaneous abortion rate. RESULT(S) The mean operative time was 63 +/- 21 minutes (95% CI, 48-143) in the LPS group and 57 +/- 23 minutes (95% CI, 38-121) in the LPT group. The mean length of hospital stay was statistically significantly greater in the LPT group (3.1 +/- 0.5; 95% CI, 1-5) than the LPS group (2.1 +/- 0.8; 95% CI, 1-4). The overall spontaneous pregnancy rate after myomectomy was 53%; the pregnancy rate after LPS myomectomy (56%) was not statistically significantly higher than the rate for LPT (50%). CONCLUSION(S) Laparoscopy showed a lower morbidity than reported for the open approach and was characterized by less blood loss and a shorter postoperative hospitalization with an higher pregnancy rate. The operating time was not much longer in the laparoscopic group, and the intraoperative and postoperative complications appeared acceptable and not more than what is traditionally expected with the open approach.

Laparoscopic Disk Resection for Bowel Endometriosis Using a Circular Stapler and a New Endoscopic Method to Control Postoperative Bleeding from the Stapler Line

BACKGROUND Complete laparoscopic excision of endometriosis offers good longterm symptomatic relief, especially for those with severe or debilitating symptoms. Intestinal endometriosis affect between 3% and 36% of women with endometriosis and 50% of women with disease severe enough that intestinal surgery, with or without intestinal segmental resection, may be required. STUDY DESIGN Between January 2003 and September 2006, we performed 35 laparoscopic complete excisions of endometriosis with full thickness disk resections of bowel endometriosis using the CEEA stapler (US Surgical) inserted transanally. RESULTS The endometriotic nodule of the bowel was completely removed in all patients. No major or minor surgical complications occurred during the primary surgical procedure. One patient underwent a diverting temporary ileostomy because of air loss after insufflation of the rectosigmoid colon, which was closed successfully 1 month after surgery. In three of seven cases of rectal bleeding from the stapler line, for the first time, we successfully used conservative endoscopic management. CONCLUSIONS In properly selected patients, full thickness disk excision using a circular stapler is a feasible procedure that avoids the potential morbidities of a low anastomosis. We suggest conservative management by endoscopic hemostasis before referring patients for a new operation in cases of rectal bleeding from the anastomotic site.

Human Chorionic Gonadotropin Protects Vascular Endothelial Cells from Oxidative Stress by Apoptosis Inhibition, Cell Survival Signalling Activation and Mitochondrial Function Protection.

Background/Aim: Previous reports have made it hypothetically possible that human chorionic gonadotropin (hCG) could protect against the onset of pregnancy-related pathological conditions by acting as an antioxidant. In the present study we planned to examine the effects of hCG against oxidative stress in human umbilical vein endothelial cells (HUVEC). Methods: HUVEC were subjected to peroxidation by hydrogen peroxide. The modulation of nitric oxide (NO) release by hCG and its effects on cell viability, glutathione (GSH) levels, mitochondrial membrane potential and mitochondrial transition pore opening (MPTP) were examined by specific dyes. Endothelial and inducible NO synthase (eNOS and iNOS), Akt and extracellular -signal-regulated kinases 1/2 (ERK1/2) activation and markers of apoptosis were analyzed by Western Blot. Results: In HUVEC, hCG reduced NO release by modulating eNOS and iNOS. Moreover, hCG protected HUVEC against oxidative stress by preventing GSH reduction and apoptosis, by maintaining Akt and ERK1/2 activation and by keeping mitochondrial function. Conclusion: The present results have for the first time shown protective effects exerted by hCG on vascular endothelial function, which would be achieved by modulation of NO release, antioxidant and antiapoptotic actions and activation of cell survival signalling. These findings could have clinical implications in the management of pregnancy-related disorders.

Laparoendoscopic single-site surgery for treatment of concomitant ovarian cystectomy and cholecystectomy.

Since the first laparoscopic appendectomy was performed by Semm in 1983, laparoscopic surgery has become the criterion standard surgical route for treatment of several pathologic conditions across disciplines. Attempts to minimize access-related injuries and complications resulted in development of laparoendoscopic single-site surgery (LESS), which, because of the decreased number of ports used, may be the next generation of minimally invasive surgery. Laparoscopic single-site surgery has been reported in nephrectomy, pyeloplasty, radical prostatectomy, cholecystectomy, and colorectal, bariatric, and gynecologic surgery. This technique may increase the benefits of traditional minimally invasive surgery such as decreased blood loss and postoperative pain, faster recovery time, fewer complications, and better cosmetic results, without increasing costs. Herein, we present a case report of single-port laparoscopic ovarian cystectomy and concomitant cholecystectomy performed with a multi-instrument access port (TriPort; Olympus America Inc., Center Valley, Pennsylvania). Single-port surgery eliminates the problem of multiple and different site placement for accessory ports, typical of these procedures when performed simultaneously at conventional laparoscopy.

Narrow Band Imaging in Endometrial Lesions

Fig. 1. Conventional hysteroscopy shows irregular polypoid hypertrophy of softened consistency. Hysteroscopy with directed biopsies has a key role in the diagnosis of intrauterine pathologies. In a series of 4054 patients, sensitivity of hysteroscopic view for endometrial cancer is 80%, suggesting that visual identification of morphologic changes in the endometrial mucosa is not always enough for a diagnostic conclusion [1]. In the literature, several studies indicate that angiogenic intensity may play a prognostic role in malignancies [2,3] and a report in 2006 showed that, in endometrial cancer, tumor-associated vessels are structurally and functionally abnormal and that structural changes are associated with increased frequency of vascular invasion and decreased survival [4]. Narrow band imaging (NBI) is a novel endoscopic technique able to enhance the accuracy of diagnosis by using narrowbandwidth filters in a red-green-blue sequential illumination system. The light penetration depth depends on the wavelength used: the blue filter is designed to correspond to the peak absorption spectrum of hemoglobin so that NBI allows appreciation of the mucosal pattern and surface microvasculature simply through an on-off switch located on the head of the endoscope. NBI appears to be a promising tool for diagnosis of gastrointestinal lesions, early detection of squamous cancer of the head-neck region, preneoplastic lesions in heavy smokers, and follow-up in patients affected by urothelial carcinoma of the bladder [5,6].

Narrow-Band Imaging in Diagnosis of Endometrial Cancer and Hyperplasia: A New Option?

STUDY OBJECTIVE To estimate whether the use of narrow-band imaging (NBI) hysteroscopy increases concordance between visual identification and a histologic diagnosis of endometrial cancer and hyperplasia. DESIGN Prospective study (Canadian Task Force classification: II-2). SETTING Department of obstetrics and gynecology, University of Eastern Piedmont, Novara, Italy. PATIENTS 209 consecutive patients with abnormal uterine bleeding. INTERVENTIONS White-light hysteroscopy and NBI hysteroscopy followed by direct biopsy. MEASUREMENTS AND MAIN RESULTS The sensitivity and specificity of conventional hysteroscopy in predicting a diagnosis of cancer and hyperplasia were, respectively, 84.21% (95% confidence interval [CI], 79.27-89.15) and 99.47% (95% CI, 98.49-100.0), and 64.86% (95% CI, 58.39-71.34) and 98.77% (95% CI, 97.27-100.0), and of NBI hysteroscopy were 94.74% (95% CI, 91.71-97.76) and 97.89% (95% CI, 95.95-99.84), and 78.38% (95% CI, 72.8-83.96) and 97.67% (95% CI, 96.63-99.72). The concordance of conventional and NBI hysteroscopy with the histopathologic findings (measured using the Cohen kappa) was, respectively, 88.80% (95% CI, 86.2%-96.3%) and 91.78% (95% CI, 89.6%-98.2%), a difference of 2.98% (95% CI, 0-9) in favor of NBI. CONCLUSION Narrow-band imaging hysteroscopy can accurately predict a histologic diagnosis of endometrial cancer or hyperplasia.

Intracoronary Des-Acyl Ghrelin Acutely Increases Cardiac Perfusion Through a Nitric Oxide-Related Mechanism in Female Anesthetized Pigs.

Des-acyl ghrelin (DAG), the most abundant form of ghrelin in humans, has been found to reduce arterial blood pressure and prevent cardiac and endothelial cell apoptosis. Despite this, data regarding its direct effect on cardiac function and coronary blood flow, as well as the related involvement of autonomic nervous system and nitric oxide (NO), are scarce. We therefore examined these issues using both in vivo and in vitro studies. In 20 anesthetized pigs, intracoronary 100 pmol/mL DAG infusion with a constant heart rate and aortic blood pressure, increased coronary blood flow and NO release, whereas reducing coronary vascular resistances (P < .05). Dose responses to DAG were evaluated in five pigs. No effects on cardiac contractility/relaxation or myocardial oxygen consumption were observed. Moreover, whereas the blockade of muscarinic cholinoceptors (n = 5) or α- and β-adrenoceptors (n = 5 each) did not abolish the observed responses, NO synthase inhibition (n = 5) prevented the effects of DAG on coronary blood flow and NO release. In coronary artery endothelial cells, DAG dose dependently increased NO release through cAMP signaling and ERK1/2, Akt, and p38 MAPK involvement as well as the phosphorylation of endothelial NO synthase. In conclusion, in anesthetized pigs, DAG primarily increased cardiac perfusion through the involvement of NO release. Moreover, the phosphorylation of ERK1/2 and Akt appears to play roles in eliciting the observed NO production in coronary artery endothelial cells.

In anesthetized pigs human chorionic gonadotropin increases myocardial perfusion and function through a β-adrenergic-related pathway and nitric oxide

Human chorionic gonadotropin (hCG) is not only responsible for numerous pregnancy-related processes, but can affect the cardiovascular system as well. So far, however, information about any direct effect elicited by hCG on cardiac function, perfusion, and the mechanisms involved has remained scarce. Therefore, the present study aimed to determine the primary in vivo effect of hCG on cardiac contractility and coronary blood flow and the involvement of autonomic nervous system and nitric oxide (NO). Moreover, in coronary endothelial cells (CEC), the intracellular pathways involved in the effects of hCG on NO release were also examined. In 25 anesthetized pigs, intracoronary 500 mU/ml hCG infusion at constant heart rate and aortic blood pressure increased coronary blood flow, maximum rate of change of left ventricular systolic pressure, segmental shortening, cardiac output, and coronary NO release (P < 0.0001). These hemodynamic responses were graded in a further five pigs. Moreover, while blockade of muscarinic cholinoceptors (n = 5) and of α-adrenoceptors (n = 5) did not abolish the observed responses, β1-adrenoceptors blocker (n = 5) prevented the effects of hCG on cardiac function. In addition, β2-adrenoceptors (n = 5) and NO synthase inhibition (n = 5) abolished the coronary response and the effect of hCG on NO release. In CEC, hCG induced the phosphorylation of endothelial NO synthase through cAMP/PKA signaling and ERK1/2, Akt, p38 MAPK involvement, which were activated as downstream effectors of β2-adrenoceptor stimulation. In conclusion, in anesthetized pigs, hCG primarily increased cardiac function and perfusion through the involvement of β-adrenoceptors and NO release. Moreover, cAMP/PKA-dependent kinases phosphorylation was found to play a role in eliciting the observed NO production in CEC.