Effects of a combination of resveratrol and alpha-lipoic acid on body weight and adipose composition in women with PCOS: a preliminary pilot study.

OBJECTIVE: Polycystic ovary syndrome is associated with reproductive and metabolic dysfunction; in fact, treatment aims in PCOS focus on optimizing healthy weight, improving underlying hormonal disturbances, preventing future reproductive and metabolic complications, and improving quality of life. PATIENTS AND METHODS: This pilot study considered 8 overweight females (BMI > 30) in reproductive age with PCOS. Patients were treated with a galenical preparation mixture containing resveratrol and alpha-lipoic acid in association with vitamin D, B and folic acid for 12 weeks, after which anthropometric assessment was conducted. RESULTS: After 12 weeks of treatment, BMI, anthropometry and bioimpedance parameters were all reduced in the treated patients compared to baseline. CONCLUSIONS: The present nutraceutical combination resulted beneficial for improving the metabolic profile of women with PCOS, paving the way for new nutraceutical strategies for the management of metabolic disturbances in PCOS.

A rare case of extrauterine schwannoma-ike leiomyoma after transvaginal hysterectomy: laparoscopic management.

Background: Schwannomas (neurilemomas) are encapsulated tumours made entirely of benign neoplastic Schwann cells. They are the most common tumour of peripheral nerves, but very uncommon in gynaecologic practice. Objectives: The objective is to demonstrate unusual histology mimicking schwannoma in a case of leiomyoma in a woman who had a history of vaginal hysterectomy. Materials and Methods: We report a case of a 50-year-old hysterectomised patient who was referred with complaints of dull pain in the left inguinal region of the abdominal cavity during the last 3 months. The narrated surgical video article demonstrates the dissection of the left parametrium, tumour removal, colpotomy, specimen extraction, and vaginal laparoscopic suturing. Pre-operative CT-scan images of the pelvis with retroperitoneal tumour and macroscopic and histological views of the schwannoma are also provided. Main outcome measures: Full recovery of the patient after laparoscopic removal of the tumour. Results: As a result of the surgical treatment, the patient recovered fully. Conclusions: Schwannoma-like leiomyomas are rare tumours. They can be extra peritoneally located, without any connection to the uterus and adnexa. They are difficult to diagnose before surgery. The laparoscopic approach is the best option for the treatment of such rare extra organic tumours.

Curcumin and Teupolioside attenuate signs and symptoms severity associated to hirsutism in PCOS women: a preliminary pilot study.

OBJECTIVE: Hirsutism affects 5-15% of women of reproductive age, with approximately 80% of these women having polycystic ovary syndrome (PCOS). The etiopathogenesis of PCOS remains unclear, the clinical characteristics of PCOS include hyperandrogenism, generally manifested as hirsutism and acne, and both these clinical symptoms are treated with oral contraceptive pills (OCPs), topical medications or antiandrogens. Curcumin (diferuloylmethane) and Plant sterols, such as a phenylpropanoid glycosides of Ajuga reptans, known as Teupolioside, have attracted considerable attention due to their pharmacological properties. Taking into consideration wide-ranging pharmacological and biological properties and the safety of herbal extracts, we proposed a combination of curcumin and teupolioside to evaluate the anti-androgenic properties in women with PCOS and clinical signs of hyperandrogenism. PATIENTS AND METHODS: Six hyperandrogenic PCOS women with a hirsutism score (HS) > 20, according to Ferriman-Gallwey scoring system, were involved in the study. These women were treated with a galenical preparation mixture containing curcumin and teupolioside and clinical features were assessed after 12 weeks. RESULTS: The nutraceutical combination containing curcumin/teopolioside ameliorated clinical manifestations associated to hyperandrogenism in women with PCOS after a 12-weeks treatment. CONCLUSIONS: This pilot study suggests that a curcumin/teopolioside nutraceutical combination is beneficial for improving various clinical manifestations associated to abnormal hormonal parameters in PCOS women, as well as signs and symptoms associated to hyperandrogenism.

The Role of Surgeons' Colposcopic Experience in Obtaining Adequate Samples by Large Loop Excision of the Transformation Zone in Women of Reproductive Age.

Introduction: There is insufficient reporting on the level of colposcopic training for the safe use of large loop excision of the transformation zone. The aim of this study was to perform a quality assessment of large loop excision of the transformation zone in women of reproductive age by evaluating the surgeons' colposcopic experience. Materials and Methods: A retrospective cohort study was performed on diagnostic or therapeutic large loop excision of the transformation zone. The following variables were analyzed: age, parity, indications for surgery, level of surgeon's colposcopic experience, definitive histological diagnosis, margin involvement, and the presence and type of artifacts interfering with the pathological interpretation. Patients were divided into three groups: group A - 75 patients treated by junior colposcopists; group B - 74 patients treated by experienced colposcopists, and group C - 117 patients treated by expert colposcopists. Results: Regarding the presence and diagnostic significance of the artifacts the groups were significantly different. Inadequate samples were the least frequent in group C. Artifacts precluding histological diagnosis were the most common in group A. The margins were predominantly inconclusive in group A. Conclusions: A high rate of artifacts is a disadvantage of the large loop excision of the transformation zone performed by surgeons less skilled for colposcopy. Although large loop excision of the transformation zone is considered to be a minor surgery, skills in colposcopy are an essential prerequisite for optimal results.

Asymptomatic isthmico-cervical uterine perforation with IUD - our experience and literature review.

PURPOSE: The study aim was to report an unusual case of a misplaced IUD in isthmico-cervical region causing partial uterine perforation and discuss literature data regarding such a condition. CASE REPORT: A 50-year-old women was referred to the present institution for IUD extraction. She was diagnosed with spontaneously misplaced IUD located in isthmico-cervical region of the uterus causing partial perforation. The time of dislocation was unknown, as she was completely asymptomatic for ten years after IUD application. More-over, she had no risk factors for device misplacement. The removal of IUD was uneventful. CONCLUSION: Isthmico-cervical misplacement of IUD, although rare, can occur at any time and can be asymptomatic. Thus, women with IUD should be annually checked-up in order to prevent possible IUD complications.

Missense mutations in exon 2 of the MED12 gene are involved in IGF-2 overexpression in uterine leiomyoma.

Uterine leiomyoma (UL), the most common benign tumour found in females, is associated with many recurrent genetic aberrations, such as translocations, interstitial deletions and specific germline mutations. Among these, mutations affecting exon 2 of the mediator complex subunit 12 (MED12) gene are commonly detected in the majority of ULs. Mutational analysis of the MED12 gene, performed on 36 UL samples, revealed that 12 leiomyomas (33.4%) exhibited heterozygous missense mutations in codon 44 of exon 2 of the MED12 gene, four leiomyomas (11.1%) showed internal in-frame deletions, and two leiomyomas (5.5%) exhibited deletions involving intron 1-exon 2 junction, which caused a predicted loss of the splice acceptor. No mutations were detected in uterine myometrium (UM) and pseudocapsule (PC) samples, including those from women with a MED12 mutation in UL. These data showed that the PC is a healthy tissue that surrounds the UL to maintain UM integrity. Analysis of insulin-like growth factor 2 (IGF-2) and collagen type IV alpha 2 (COL4A2) mRNA expression levels in the same set of ULs revealed that only those with MED12 missense mutations expressed significantly higher levels of IGF-2 mRNA. In contrast, MED12 gene status does not appear to affect mRNA expression levels of the COL4A2 gene. On the basis of this finding, we suggest that the MED12 status stratifies the ULs into two mutually exclusive pathways of leiomyoma genesis, one with IGF-2 overexpression and the other with no IGF-2 activation. The occurrence of IGF-2 overexpression could be therapeutically targeted for the non-surgical treatment of leiomyomas.

The anaesthetic and recovery profile of two concentrations (0.25% and 0.50%), of intrathecal isobaric levobupivacaine for combined spinal-epidural (CSE) anaesthesia in patients undergoing modified Stark method caesarean delivery: a double blinded randomized trial.

BACKGROUND: In spinal anaesthesia for a Caesarean delivery, it is important to limit anaesthesia only at the surgical area, and to resolve fast motor block. We compared the intraoperative effectiveness, hemodynamic effects, anaesthetic recovery times and patients satisfaction after isobaric levobupivacaine (L) 0.25% versus L0.50% spinal anaesthesia during elective Caesarean deliveries performed with the Stark technique. PATIENTS AND METHODS: In this double-blinded prospective study, seventy women undergoing elective caesarean delivery were randomized to receive either intrathecal 7.5 mg Levobupivacaine 0.25% plus sufentanil 2.5 µg (Group L0.25), or intrathecal 7.5 mg L 0.50% plus sufentanil 2.5 µg (GroupControl). The onset time, duration of anaesthesia, analgesia and sensory and motor block and hemodynamic parameters were measured from the beginning of spinal anaesthesia until four hours after spinal anaesthesia (T240). RESULTS: Onset time, duration of anaesthesia and haemodynamic variations were similar in the two groups. No patients required general anesthesia to complete surgery. Motor block vanished faster in Group L0.25 as compared with GroupControl (p < .01). The cephalad spread of the 0.50% solution was higher than that of the 0.25% solution: no patient in Group L0.25 experienced paresthesia of the upper limbs vs 14% in GroupControl (p < .05). In GroupControl anaesthesia reached the dermatome T1 in 15% of cases. Maternal and surgeon satisfaction was good in every patient. CONCLUSIONS: Levobupivacaine 7.5 milligrams at 0.25% may be used as a suitable alternative to L 0.50% for spinal anaesthesia for caesarean deliveris with the Stark technique with good maternal satisfaction. In Group L0.25 a lower appearance of nausea and hypotension were observed and motor and sensitive block developed and diminished faster while no clinically significant differences in hemodynamic behavior was observed between groups.

Gene expression analysis reveals an angiogenic profile in uterine leiomyoma pseudocapsule.

The pseudocapsule (PC) of the uterine leiomyoma (UL) is an anatomic entity that surrounds the myoma separating it from the myometrium (UM). Although a number of microarray experiments have identified differences in gene expression profile in the UL when compared with the UM, there is a lack of systematic studies on the PC. In this study, quantitative RT-PCR analysis was performed on 18 matched PC, UL and UM specimens and results showed that the PC displays a specific gene expression profile. The low expression level of insulin-like growth factor (IGF-2), a fibroid specific marker, that we found in the PC and the UM when compared with the UL, clearly indicates that the PC is in structural continuity with the UM. However, the significant increase in endoglin expression level in PC with respect to the UL and UM indicates that an active neoangiogenesis is present in PC. Conversely, other angiogenic factors such as von Willebrand factor (vWF) and vascular endothelial growth factor A (VEGF-A) seem to have little influence on the PC angiogenesis. Because the endoglin is preferentially expressed in proliferating endothelial cells, whereas the vWF and VEGF-A are preferentially expressed in preexisting endothelial cells, our idea is that the angiogenic activity in the PC is linked to wound healing. The angiogenic activity is also sustained by intermediate expression level of cystein-rich angiogenesis inducer 61, connective tissue growth factor and collagen 4α2 genes all involved in the neoangiogenesis, that we detected in the PC. Taken together our data demonstrate that the specific expression pattern observed in the PC could be the response of the uterine wall's smooth cells to the tension imposed by the tumor. As a consequence, a neovascular structure is generated involving regenerative processes. For these reasons, we suggest that the laparoscopic intracapsular myomectomy (LIM), a new surgical technique that preserves the PC during the UL removal, should always be preferred, to favor a faster and proper uterine healing.

The impact of proteomics in the understanding of the molecular basis of Paclitaxel-resistance in ovarian tumors.

The current therapy for ovarian cancer has advanced from alkylating agents, to a combination of carboplatinum and paclitaxel offering increased survival. Although most patients respond to this first-line therapy, initially, the majority of these patients relapse within 2 years. The mechanisms responsible for acquired drug resistance in ovarian cancer have been elucidated only in part. They include i) enhanced drug export, ii) activation/inhibition of intracellular signalling pathways, iii) molecular alterations in tubulin isotype composition. A better understanding of these mechanisms is needed, in order to develop new approaches, aimed at overcoming resistance to anticancer agents, and to reveal the complexity of causes, which contribute to drug resistance. In this review we offer an updated overview of proteomic studies on the molecular mechanisms of paclitaxel resistance. These proteomic studies also identify potential targets for modulating drug resistance, that could be predictive of response to chemotherapy in ovarian carcinomas.

Suprapubic percutaneous sclero-embolization of symptomatic female pelvic varicocele under local anesthesia.

PURPOSE: To evaluate the safety and feasibility of supra-pubic percutaneous sclero-embolization (SE) in the treatment of symptomatic female pelvic varicocele (FPV), performed under local anesthesia. MATERIALS AND METHODS: The authors selected 28 patients screened by transabdominal and transvaginal ultrasound, with venous Doppler signal. Clinicians performed SE by transfemoral catheterization, under local anesthesia, using of a mix of 2 ml of lauromacrogol 400 (Atossisclerol 3%, Chemische F. Kreussler, Wiesbaden, Germany) and 2 ml of air, in a mixed foam fashion. RESULTS: The total operative time for SE was 7.6 +/- 2.1 min. Intra-surgical blood loss was 40 +/- 14 ml. No migration of sclerosant material occurred and postoperative analgesic request during a 48 hr period occurred in 6 patients. Technical success was 100%. The Authors embolized 8 women bilaterally (28.5%), 18 on the left ovarian vein (OV) (64.2%) and 2 only in the right OV (7.1%): 7 women complained of transitory flank pain (25%), which disappeared in few minutes. The major complications in 10 days after SE were: fever (> 38 degrees C for two days) in 2 patients (7.1%) and pelvic pain for 3 days in eight patients (28.5%). After 30 days only 6 women suffered of FPV lower symptoms which disappeared in 180 days. A substantial reduction in size of pelvic varicosities was noted in all patients. CONCLUSIONS: SE is a safe and feasible procedure. It reduces significantly the mean time of scopies, the intensity of radiation emission, and it is performed under local anaesthesia. This minimally invasive procedure could be proposed to all women with supra-pubic FPV for its reproducibility and feasibility.

Salvage utilization of selective and super selective embolization in emergency by use of a-magnetic coil and nano-particles in gynecology.

INTRODUCTION: Pelvic arteries embolization (PAE) can be described as an obstetric procedure effective in emergencies, to use especially in managing uncontrollable acute uterine hemorrhage, if resistant to medical therapy. This procedure leads to immediate control of hemorrhages and restores cardiovascular status, especially in critical patients. PAE can be used as an alternative to removing organs. PURPOSE OF STUDY: To utilize the PAE in local anesthesia for management of acute uterine hemorrhage for cervical myoma in a critical patients, a fertile woman with concomitant cardiovascular stroke and in high-dosage of antithrombosis therapy, with severe anemia. MATERIAL ANDS METHODS: This procedure was used in an University affiliated Hospital, by a selective catheterization of the left hypogastric artery with an a-magnetic coil and super-selective catheterization of the right uterine artery, instilling a mixture of micro-particles and an absorbable haemostatic gelatin. RESULTS: Authors have successfully completed this procedure in 40 minutes in local anaesthesia, showed by stopping of iodated contrast fluid in vascular myoma network, with subsequent cervical myomectomy, whilst preserving uterus. CONCLUSION: PAE allows, through super-selective catheterization of both uterine arteries or selective catheterization of hypogastric arteries, to instill a mixture of micro-particles, absorbable haemostatic gelatins or endovascular coils, mixed with iodated contrast fluid and, thereby, to stop bleeding. This procedure leaded to an immediate control of hemorrhages and restores cardiovascular status, as an alternative to removing organs.

Surgical technique to avoid bladder flap formation during cesarean section.

Cesarean section (CS) is now the most common major surgical procedure performed on women worldwide. A CS can be performed by either suturing or not suturing of the visceral peritoneum. Creation of the bladder flap is an integral step of the standard cesarean section. The bladder flap is made by superficially incising and dissecting the peritoneal lining to separate the urinary bladder from the lower uterine segment. It's still debated whether the formation of bladder flap is advantageous or not. If the uterine incision is made slightly above the vesicouterine peritoneal fold, the loose connective tissue between the uterus and the urinary bladder allows spontaneous descent of the bladder. Evidence on the role of the bladder flap in cesarean section is very limited. At present, it remains to be established whether there is any advantage in dissecting the bladder from the lower uterine segment during cesarean section.

Lapatinib in breast cancer: clinical experiences and future perspectives.

Lapatinib, an orally available dual inhibitor targeting the tyrosine-kinase domain of both epidermal growth factor receptor-1 and 2, has been introduced for the treatment of advanced/metastatic HER2+ breast cancer in combination with capacitabine after chemotherapy regimens containing anthracycline, taxanes and trastuzumab. Moreover, lapatinib is under investigation in combination with anthracycline and taxanes in neoadjuvant and adjuvant settings. Another potential field of investigation for this drug is related to its ability to restore hormonal sensitivity of HER2-, hormone-receptor positive breast cancer cells. This paper reviews the current use of lapatinib in breast cancer and its future perspectives.

Microsatellite instability (MSI) as genomic markers in endometrial cancer: toward scientific evidences.

Endometrial Cancer is the most frequent tumor in western world nations, with 142,000 new cases each year and 42,000 casualties. This form of cancer typically affects women between 55 and 65 years of age, and ranks fourth among female tumors. Endogenous predisposing conditions to endometrial cancer development are: late menopause, early menarche and hyperestrogenism, while hormone replacement therapy, obesity, alcohol, diabetes, and a diet rich in animal fats as well as chronic liver disease, are the exogenous factors. This tumor may also have an hereditary predisposition, as in the Lynch Syndrome or in HNPCC (Hereditary NonPolyposis Colorectal Cancer), since genetic modifications induced by the "MisMatch Repair" genes lead to a tumoral development susceptibility, not only in the colon. The phenotypical consequences of these genetic modifications may be found in the microsatellite instability (MSI) and in the loss of heterozygosity (LOH), which generate the replication errors in positive phenotypes repeats. These express the incapability to repair short nucleotide insertions or deletions, generated by a wrong DNA replication. Due to such genetic modifications, new allelic variants arise in the endometrial tissue, confirming the high degree of this genetic disorder. Recent studies showed that the MSI and LOH in endometrial cells may be associated with the possible loss in the expression of cellular control and with the possible degeneration of the cell growth phenomenon. There is also a possibility of utilizing these new genetic markers in the endometrial mucosa to study these tissues and to detect any possible neoplastic transformations, thanks to Genomics.

Low-dose sequential combined spinal-epidural anaesthesia in elective Stark caesarean section: a preliminary cohort study.

AIM: To compare combined spinal-epidural anaesthesia (CSE) VS spinal anaesthesia (SA) in caesarean section (CS) performed by Stark method. MATERIAL AND METHODS: 200 women were prospectively studied before undergoing to a Stark CS in two groups: 95 patients were assigned to a local anaesthesia by SA (first group) and 105 women to CSE anaesthesia (second group). After a pre-load of 500 ml of plasma expander in both groups, SA was performed at the L1-L2 interspace with an injection of 5 ml of levobupivacaine 0.15%, with a 5 mcg of Sufentanil. The CSE was performed by a spinal-epidural injection at the L1-L2 interspace, primarily by 4 ml of levobupivacaine 0.125% and 5 mcg of Sufentanil, then by 3-7 mL of xilocaine carbonate 0.5% plus 1 mcg/ml of Sufentanil. Successively a CS by Stark method was performed in both groups. The recorded anaesthesiologic side effects in two groups were: motor block, intraoperative discomfort, vomiting, bradycardia and hypotension. Statistical evaluation was by Z-Test referred to the comparison of 2 portions with great, independent samples. RESULTS: In the group with CSE anaesthesia, the prevalence of side effects was less than in the group treated with SA, where the prevalence of the motor block and intraoperative discomfort were greater and statistically significant (p<0.001); so as the vomiting and bradycardia were all in a major percentage in SA group, but only significant for hypotension (p<0.001). CONCLUSIONS: These preliminary data show that the association between CS and CSE anaesthesia in elective CS by Stark method allow to have less intra and post-operative side effects; further studies need to provide specific details on the anaesthetic and surgical techniques, to tailor and optimize both in each patient to select for surgery.