Raf kinase inhibitor protein expression in smooth muscle tumours of the uterus: a diagnostic marker for leiomyosarcoma?

RESEARCH QUESTION: What is the expression pattern of Raf kinase inhibitory protein (RKIP) in different subtypes of leiomyoma (usual type, cellular, apoplectic or haemorrhagic leiomyoma, leiomyoma with bizarre nuclei and lipoleiomyoma) and leiomyosarcoma specimens, and what is its biological role in leiomyosarcoma cells? DESIGN: Leiomyoma and leiomyosarcoma specimens underwent immunohistochemistry staining. Leiomyosarcoma SK-LMS-1 cell line was RKIP knocked down and RKIP overexpressed, and cell viability, wound healing migration and clonogenicity assays were carried out. RESULTS: A higher immunohistochemical expression of RKIP was observed in bizarre leiomyomas, than in usual-type leiomyomas. Decreased expression was also found in cellular leiomyoma, with generally absent staining in leiomyosarcomas. Upon RKIP expression manipulation in SK-LMS-1 cell line, no major differences were observed in cell viability and migration capacity over time. RKIP knockout, however, resulted in a significant increase in the cell's ability to form colonies (P = 0.011). CONCLUSION: RKIP distinct expression pattern among leiomyoma histotype and leiomyosarcoma, and its effect on leiomyosarcoma cells on colony formation, encourages further studies of RKIP in uterine smooth muscle disorders.

A Longitudinal Multiinstitutional Study of Vulvar Lichen Sclerosus: From Childhood to Perimenopause.

OBJECTIVE: The main outcome of this study was the evaluation of clinical characteristics, comorbidities, and therapeutic approaches in patients with vulvar lichen sclerosus (VLS) aged from childhood to perimenopause. Secondly, it was intended to compare these characteristics according to the menarchal status. METHODS: Patients less than 45 years of age with a diagnosis of VLS from January 2002 to June 2022 in 10 referral centers were included in this retrospective longitudinal study. The univariate analysis compared the dependent variables according to menarchal status. RESULTS: One hundred eighty-six patients met the inclusion criteria. At diagnosis, between 25% and 40% of premenarchal patients reported signs related to subepithelial hemorrhage. A significantly greater presence of bleeding ( p < .005), easy bruising ( p = .028), fissures ( p = .008), petechiae/splinter hemorrhages ( p < .001), and bleeding/blistering or open sores ( p = .011) was observed in premenarchal patients with respect to the postmenarchal group. The perineum ( p = .013) and the perianal region ( p < .001) were significantly more involved in the premenarchal group. Topical calcineurin inhibitors were more used in the premenarchal population ( p = .004), whereas vitamin E oil and moisturizers were more used in the postmenarchal population ( p = .047). CONCLUSIONS: Vulvar lichen sclerosus is a chronic condition that can cause vulvar changes that result in severe morbidity and affects sexual function and quality of life, even before menopause. Vulvar lichen sclerosus continues to be misdiagnosed in this population. This may lead to an average delay from symptom onset to diagnosis. Evaluating clinical manifestations of VLS in premenarchal and postmenarchal age allowed us to find different clinical characteristics between the 2 periods suggestive of the diagnosis.

High levels of hypusinated eIF5A in leiomyoma and leiomyosarcoma pathologies: a possible novel therapeutic target.

RESEARCH QUESTION: Is the hypusinated form of the eukaryotic translation initiation factor 5A (EIF5A) present in human myometrium, leiomyoma and leiomyosarcoma, and does it regulate cell proliferation and fibrosis? DESIGN: The hypusination status of eIF5A in myometrial and leiomyoma patient-matched tissues was evaluated by immunohistochemistry and Western blotting as well as in leiomyosarcoma tissues by immunohistochemistry. Myometrial, leiomyoma and leiomyosarcoma cell lines were treated with N1-guanyl-1,7-diaminoheptane (GC-7), responsible for the inhibition of the first step of eIF5A hypunization, and the proliferation rate was determined by MTT assay; fibronectin expression was analysed by Western blotting. Finally, expression of fibronectin in leiomyosarcoma tissues was detected by immunohistochemistry. RESULTS: The hypusinated form of eIF5A was present in all tissues examined, with an increasing trend of hypusinated eIF5A levels from normal myometrium to neoplastic benign leiomyoma up to neoplastic malignant leiomyosarcoma. The higher levels in leiomyoma compared with myometrium were confirmed by Western blotting (P = 0.0046). The inhibition of eIF5A hypusination, with GC-7 treatment at 100 nM, reduced the cell proliferation in myometrium (P = 0.0429), leiomyoma (P = 0.0030) and leiomyosarcoma (P = 0.0044) cell lines and reduced the expression of fibronectin in leiomyoma (P = 0.0077) and leiomyosarcoma (P = 0.0280) cells. The immunohistochemical staining of leiomyosarcoma tissue revealed that fibronectin was highly expressed in the malignant aggressive (central) part of the leiomyosarcoma lesion, where hypusinated eIF5A was also highly represented. CONCLUSIONS: These data support the hypothesis that eIF5A may be involved in the pathogenesis of myometrial benign and malignant pathologies.

Gestational Diabetes Mellitus and Small-for-Gestational-Age: An Insight into the Placental Molecular Biomarkers.

Gestational diabetes mellitus (GDM) and small-for-gestational-age (SGA) are two metabolic-related diseases that could affect women during pregnancy. Considering that the chorionic villi (CVs) are crucial structures for the feto-maternal exchange, the alterations in their conformation have been linked to an imbalanced metabolic environment of placenta. In this study, a multidisciplinary approach has been carried out to describe the changes occurring in the placental CVs of GDM and SGA patients. The results revealed higher levels of superoxide dismutase 1 (SOD-1) and catalase (CAT), especially in the GDM placentae, which could be correlated with the hyperglycemic environment characteristic of this pathology. Furthermore, spectroscopy and histologic analyses revealed that both pathologies modify the placental lipid composition altering its structure. However, SGA induces lipid peroxidation and reduces collagen deposition within the CVs. Since the endocannabinoid system (ECS) is involved in placentation and different metabolic activities, the cannabinoid receptor 1 (CB1) and transient receptor potential cation channel subfamily V member 1 (TRPV-1) were analyzed. No changes have been observed either at general or specific levels in the CVs comparing control and pathological samples, suggesting the non-involvement of the cannabinoid system in these two pathologies.

Homozygous C677T Methylenetetrahydrofolate Reductase (MTHFR) Polymorphism as a Risk Factor for Endometriosis: A Retrospective Case-Control Study.

This study was conducted to evaluate the role of methylenetetrahydrofolate reductase (MTHFR) C677T homozygous polymorphism as a risk factor for endometriosis. A retrospective case-control study was conducted from January 2020 to December 2022 on all patients attending the gynecological outpatient clinic of our institution who had performed an MTHFR polymorphisms test. Patients with endometriosis were considered cases, while those without endometriosis were considered controls. The presence of an MTHFR C677T homozygous polymorphism was defined as exposure. Risk factors for endometriosis were considered confounders in a binomial logistic regression, with endometriosis diagnosis as the dependent variable. Among the 409 included patients, 106 (25.9%) cases and 303 (74.1%) controls were identified. A higher rate of MTHFR C677T homozygous polymorphism was found in patients with endometriosis (24.5% vs. 15.8%, p = 0.0453), with an adOR of 1.889 (95% CI 1.076-3.318, p = 0.0269) at the binomial logistic regression. A history of no previous pregnancy was associated with an endometriosis diagnosis (adOR 2.191, 95% CI 1.295-3.708, p = 0.0035). An MTHFR C677T homozygous polymorphism could be considered a risk factor for endometriosis. Epigenetic modifications may be the most important mechanism explaining the observed association through the processes of altered DNA methylation and reduced activity of antioxidant systems.

Uterine fibroid vascularization: from morphological evidence to clinical implications.

Uterine fibroids are the most common cause of solid pelvic tumours, occurring in 20-30% of fertile women and presenting clinical complications that seriously affect women's health. They commonly cause severe symptoms, such as heavy, prolonged menstrual bleeding and anaemia. The study of microscopic and macroscopic vascular aspects of uterine fibroids is important for understanding the clinical manifestations of uterine fibroids, for predicting the effectiveness of alternative treatments to surgery, i.e. uterine artery embolization, for improving surgery outcomes and for carrying out a differential diagnosis with other benign conditions, e.g. adenomyosis, or malignancy, e.g. leiomyosarcoma, and to develop new therapeutic approaches. In this review, current knowledge of how the vascular network and angiogenesis are implied in the formation of uterine fibroids and in the pathogenesis of related symptoms is explored, and evidence on the role of ultrasound in evaluating fibroid vascularization is summarized. This review combines anatomical, morphological and biomolecular information related to angiogenic mechanisms with diagnostic and clinical information, highlighting the various interconnections. Uterine and fibroid vascularization need further investigation to gain a deeper understanding of the pathogenetic elements that lead to the formation of uterine fibroids and their clinical manifestations.

Pathogenic Role of the Sphingosine 1-Phosphate (S1P) Pathway in Common Gynecologic Disorders (GDs): A Possible Novel Therapeutic Target.

Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid, noteworthy for its involvement both in the modulation of various biological processes and in the development of many diseases. S1P signaling can be either pro or anti-inflammatory, and the sphingosine kinase (SphK)-S1P-S1P receptor (S1PR) axis is a factor in accelerating the growth of several cells, including endometriotic cells and fibrosis. Gynecologic disorders, including endometriosis, adenomyosis, and uterine fibroids are characterized by inflammation and fibrosis. S1P signaling and metabolism have been shown to be dysregulated in those disorders and they are likely implicated in their pathogenesis and pathophysiology. Enzymes responsible for inactivating S1P are the most affected by the dysregulation of S1P balanced levels, thus causing accumulation of sphingolipids within these cells and tissues. The present review highlights the past and latest evidence on the role played by the S1P pathways in common gynecologic disorders (GDs). Furthermore, it discusses potential future approaches in the regulation of this signaling pathway that could represent an innovative and promising therapeutical target, also for ovarian cancer treatment.

HPV-Negative Adenocarcinomas of the Uterine Cervix: From Molecular Characterization to Clinical Implications.

Cervical cancer is the fourth most common cancer in women. It is the leading cause of female deaths in developing countries. Most of these cervical neoplasms are represented by squamous lesions. Cervical adenocarcinoma causes about a quarter of cervical cancers. In contrast to squamous lesions, cervical glandular disease is HPV-negative in about 15-20% of cases. HPV-negative cervical adenocarcinomas typically present in advanced stages at clinical evaluation, resulting in a poorer prognosis. The overall and disease-free survival of glandular lesions is lower than that of squamous lesions. Treatment options require definitive treatments, as fertility-sparing is not recommended. Moreover, the impact of HPV vaccination and primary HPV screening is likely to affect these lesions less; hence, the interest in this challenging topic for clinical practice. An updated review focusing on clinical and molecular characterization, prognostic factors, and therapeutic options may be helpful for properly managing such cervical lesions.

Preeclampsia Correlates with an Increase in Cannabinoid Receptor 1 Levels Leading to Macromolecular Alterations in Chorionic Villi of Term Placenta.

Preeclampsia is a human pregnancy-specific disease characterized by abnormal placentation that usually presents with maternal hypertension and proteinuria. The main hallmark of preeclampsia, impaired trophoblast migration, and the subsequent disruption of uterine arteries remodeling lead to several molecular alterations in the placental compartments with those occurring in the chorionic villi being of the utmost importance. Given the essential role of the endocannabinoid system during preimplantation and trophoblast migration, we have combined the histological and hyperspectral imaging analyses to shed light on the involvement of two cannabinoid receptors in the macromolecular alterations related to preeclampsia. The results obtained by immunohistochemistry showed a significant increase in the protein levels of cannabinoid receptor 1 (CB1) in the preeclamptic chorionic villi. However, no changes were reported regarding transient receptor potential vanilloid 1 (TRPV-1) levels either in the bulk placental samples or chorionic villi when comparing control and preeclamptic patients. Histological analysis and Fourier-transform infrared spectroscopy (FTIRI) showed an increase in collagen deposition together with higher levels of lipid peroxidation and phosphorylated compounds in the pathological villi. Since CB1 enhancement has been described as promoting fibrosis and oxidative stress in several tissues, we proposed that the higher receptor abundance in preeclampsia could be triggering similar molecular effects in preeclamptic term placentas.

Factors influencing intraoperative blood loss and hemoglobin drop during laparoscopic myomectomy: a tailored approach is possible?

A retrospective study was conducted on patients subjected to laparoscopic myomectomy at our institution from January 2017 to December 2018 to identify predictive factors of blood loss. Two multiple regression models were run to predict intraoperative blood loss and haemoglobin drop. Predictors of an increased intraoperative blood loss and haemoglobin drop were the presence of three-four fibroids at ultrasound (+47 ml, p = .01; +0.58 g/dl, p = .05) and increased operative time (r = 0.57, p = .01; r = 0.01, p < .01), while predictors of a reduced intraoperative blood loss and haemoglobin drop were epinephrine injection (-50 ml, p < .01; -0.42 g/dl, p < .01), FIGO7 (-87 ml, p < .01; -0.85, p = .01), and FIGO6 (-35 ml, p < .01; -0.44, p = .02) fibroids at the ultrasound. Preoperative ultrasound evaluation is crucial in identifying patients at higher risk for blood loss, which could benefit from optimising haemoglobin values. The injection of diluted epinephrine could be proposed in selected high-risk patients. In the clinical practice, a tailored approach based on fibroids' ultrasonographic characteristics should be implemented to optimise preoperative Hb values and evaluate the use of diluted epinephrine in selected cases, reducing blood loss and the potential related complications.Impact statementWhat is already known on this subject? Laparoscopic myomectomy is the conservative surgical treatment of choice for symptomatic uterine fibroids. Still, it could represent a challenging procedure even for an experienced surgeon, with the risk of excessive blood loss, need of transfusions, prolonged operative time, and prolonged hospital stay. The knowledge of the predictive factors of blood loss is essential for patient preparation and surgical planning to reduce intraoperative and postoperative complications.What do the results of this study add? The results of the present study focus on the importance of presurgical evaluation to identify predictive factors of intraoperative blood loss and Hb drop such as the number of fibroids and the FIGO classification (at preoperative ultrasound), as well as intraoperative factors like operative time and the intramyometrial injection of diluted epinephrine.What are the implications of these findings for clinical practice and/or further research? A tailored approach based on the ultrasonographic characteristics of fibroids should be implemented to optimise preoperative haemoblobin levels.

Age-related distribution of uncommon HPV genotypes in cervical intraepithelial neoplasia grade 3.

AIM: Cervical cancer prevention guidelines include Human Papillomavirus (HPV) test, cytology, and HPV-16/18 typing for triage to determine the risk of cervical intraepithelial neoplasia (CIN) grade 3 as the best proxy of cervical cancer risk. In doing that, they do not consider how age can modify the type-specific risk of CIN3. The present study aimed to evaluate the age-related distribution of HPV genotypes affecting the risk-assessment in cervical cancer screening programs: non-screening-type-HPV and non-HPV-16/18 in unvaccinated women with CIN3. METHODS: Retrospective multi-institutional study, including HPV genotyped women with CIN3 on cone histology treated between 2014 and 2019. The sample was divided into three categories of age: <30, 30-44, ≥45. HPV genotypes were grouped in non-screening-type-HPV (not-including genotypes 16/18/31/33/35/39/45/51/52/56/58/59/66/68) and non-HPV-16/18. Associations and trends between different age-groups and HPV genotypes were measured. RESULTS: 1332 women were analyzed. Non-screening-type-HPV CIN3 were 73 (5.5%). Non-HPV-16/18 were found in 417 participants (31.3%). Women over 45 associated with non-screening-type HPV [odds ratio (OR) = 1.87, 95% confidence interval (CI) 1.07-3.25; p = 0.027]. Non-screening-type-HPV prevalence increased significantly with age (3.9% vs 5.1% vs 9.0%, p = 0.016). Women under 30 showed a lower rate of non-HPV-16/18 (OR = 0.65, 95% CI 0.47-0.89; p = 0.007). There was a positive trend with age of non-HPV-16/18 CIN3 (23.6% vs 32.1% vs 38.0%, p = 0.0004). CONCLUSION: The proportion of CIN3 lesions unrelated to genotypes detected by primary screening tests increased with age. This implies that age probably modifies the risk of CIN3 and possibly of cancer associated with HPV types. The risk-based recommendation should take into consideration age to define the management of HPV positive women.

Quercetin and indole-3-carbinol inhibit extracellular matrix expression in human primary uterine leiomyoma cells.

RESEARCH QUESTION: What is the effect of quercetin and indole-3-carbinol (I3C) on extracellular matrix expression, cell migration and proliferation in human myometrial and uterine leiomyoma cells. DESIGN: Myometrial and leiomyoma cells were treated with quercetin or I3C at different concentrations (10 µg/ml; 50 µg/ml; 100 µg/ml; and 250 µg/ml) for 48 h to measure mRNA and protein expressions of extracellular matrix (collagen 1A1, fibronectin and versican), as well as cell migration and the proliferation rate. RESULTS: Quercetin decreased mRNA levels of collagen 1A1 in myometrial (P < 0.0001) and leiomyoma cells (P < 0.0001). Quercetin reduced mRNA and protein levels of fibronectin in myometrial cells (P < 0.05) and fibronectin protein in leiomyoma cells (P < 0.05). I3C reduced collagen 1A1 mRNA levels in myometrial (P < 0.05) and leiomyoma cells at higher dose (P < 0.05). The protein levels of fibronectin were also reduced in both myometrial and leiomyoma cells with highest dose of I3C (P < 0.05), although mRNA levels were not affected in leiomyoma cells. Neither quercetin nor I3C treatment altered versican mRNA levels in both cell types. A significant reduction of the migration of both myometrial and leiomyoma cells in response to quercetin was observed (P < 0.05) and I3C (P < 0.05 for myometrial and P < 0.01 for leiomyoma cells) treatment. Both quercetin and I3C significantly reduced myometrial cell proliferation (P < 0.05). CONCLUSIONS: The in-vitro anti-fibrotic, anti-migratory and anti-proliferative effects of quercetin and I3C form the scientific basis for developing new therapeutic, preventive agents, or both, for uterine leiomyomas.

From 2646 to 15: differentially regulated microRNAs between progenitors from normal myometrium and leiomyoma.

BACKGROUND: Uterine leiomyomas (fibroids) are smooth muscle neoplasms of the myometrial layer of the uterus and are the most common benign tumors in women. Although their etiology is still unclear, progenitor cells seem to be implicated. OBJECTIVE: To identify the dysregulated pathways involved in leiomyoma onset by microRNA profiling of progenitor cells isolated from normal myometrium and leiomyoma tissue. MATERIALS AND METHODS: Pairs of normal myometrium and uterine fibroid specimens were collected from 12 myomectomy patients. Myometrial progenitor cells and leiomyoma progenitor cells were isolated and characterized for stemness. After total RNA extraction and profiling of their 2646 microRNAs, DIANA-miRPath analysis was applied to find any dysregulated pathways. RESULTS: Only 30 microRNAs showed a significant differential regulation between myometrial progenitor cells and leiomyoma progenitor cells. Removal of those that had values close to the cut-off or that were not consistent among triplicates left 15 microRNAs, of which 7 were downregulated and 8 were upregulated in leiomyoma progenitor cells compared to myometrial progenitor cells. According to DIANA-miRPath analysis, the 7 downregulated microRNAs (hsa-miR-146b-5p; hsa-miR-335-3p; hsa-miR-335-5p; hsa-miR-135b-5p; hsa-miR-10a-3p; hsa-miR-10a-5p; hsa-miR-200a-3p) are all related to 3 pathways, "ECM-receptor interaction" (33 targeted genes), "Adherens junction" (33 targeted genes), and "Hippo signaling" (69 targeted genes), whereas the 8 upregulated miRNAs (hsa-miR-146a-5p; hsa-miR-576-3p; hsa-miR-122-5p; hsa-miR-1246; hsa-miR-595; hsa-miR-658; hsa-miR-4284; hsa-miR-924) are related to 4 pathways, "PI3K-Akt signaling pathway" (71 targeted genes), "Pathways in Cancer" (80 targeted genes), "Cell Cycle" (37 targeted genes), and "Regulation of actin cytoskeleton" (41 targeted genes). CONCLUSION: The findings that only 15 of 2646 microRNAs are differentially regulated in normal myometrium and leiomyoma and that they are involved in 7 dysregulated pathways provides interesting insights into the development of uterine fibroids, and lends support to the hypothesis that leiomyoma onset is the result of alterations affecting progenitor cells.

Clinical Characteristics and Long-Term Follow-up of Patients Treated for High-Grade Vaginal Intraepithelial Neoplasia: Results From a 20-Year Survey in Italy.

OBJECTIVES: The aim of this survey was to evaluate the different surgical approaches for women with high-grade vaginal intraepithelial neoplasia (HG-VaIN) used in 8 hospitals in central and northern Italy in the last 20 years. In particular, the baseline characteristics of the patients and factors potentially leading to excisional treatment rather than ablation were considered. Moreover, the clinical outcome of patients treated for HG-VaIN (disease persistence or recurrence and progression toward invasive vaginal cancer) was analyzed. MATERIALS AND METHODS: The medical records of all women initially diagnosed with HG-VaIN and subsequently treated in 8 Italian hospitals from January 1996 to December 2016 were analyzed in a multicenter retrospective case series. RESULTS: Among the 226 women included, 116 (51.3%) underwent ablative procedures and 110 underwent excisional surgery (48.7%). An ablative procedure was preferred in cases where multiple lesions were found on colposcopic examinations. Physicians decided more frequently to perform excisional procedures in women with menopausal status, high-grade referral cervical cytology, previous hysterectomy for human papillomavirus-related disease, or VaIN 3 on colposcopic-guided biopsy. CONCLUSIONS: The surgical treatment of HG-VaIN should be tailored according to the clinical characteristics of each woman and each lesion. However, in potentially high-risk cases (VaIN 3, previous hysterectomy for human papillomavirus-related disease, and menopausal women) or in those cases in which an occult invasive disease cannot be ruled out, an excisional approach should be preferred.In any case, long-term follow-up is advisable in women treated for HG-VaIN.

Romina: A powerful strawberry with in vitro efficacy against uterine leiomyoma cells.

Uterine leiom yomas are benign tumors highly prevalent in reproductive women. In thecurrent study, initially, we aimed to screen five different strawberry cultivars (Alba, Clery, Portola, Tecla, and Romina) to identify efficient cultivars in terms of phytochemical characterization and biological properties by measuring phenolic and anthocyanin content as well as antioxidant capacity, and by measuring apoptotic rate and reactive oxygen species (ROS) production in uterine leiomyoma cells. Next, we focused on the most efficient ones, cultivar Alba (A) and Romina (R) as well as Romina anthocyanin (RA) fraction for their ability to regulate oxidative phosphorylation (oxygen consumption rate [OCR]) glycolysis (extracellular acidification rate [ECAR]), and also fibrosis. Leiomyoma and myometrial cells were treated with a methanolic extract of A and R (250 µg/ml) or with RA (50 µg/ml) for 48 hr to measure OCR and ECAR, as well as gene expression associated with fibrosis. In the leiomyoma cells, RA was more effective in inducing apoptosis and increasing intracellular ROS levels, followed by R and A. In myometrial cells, all strawberry treatments increased the cellular viability and decreased ROS concentrations. Leiomyoma cells showed also a significant decrease in ECAR, especially after RA treatment, while OCR was slightly increased in both myometrial and leiomyoma cells. R and RA treatment significantly decreased collagen 1A1, fibronectin, versican, and activin A messenger RNA expression in leiomyoma cells. In conclusion, this study suggests that Romina, or its anthocyanin fraction, can be developed as a therapeutic and/or preventive agent for uterine leiomyomas, confirming the healthy effects exerted by these fruits and their bioactive compounds.

Factors Related to Overtreatment in the See-and-Treat Approach: A Retrospective Multicentric Observational Study.

OBJECTIVE: The aim of the study was to evaluate the association between colposcopic features, age, menopausal status, and overtreatment in women subjected to "see-and-treat" approach, to identify subgroups of patients in which this approach could be more appropriate. MATERIALS AND METHODS: Retrospective multicentric cohort study conducted on women older than 25 years, with a high-grade squamous cytological report and a visible squamocolumnar junction, in which colposcopy and the excisional procedure were performed at the same time without a previous cervical biopsy (see and treat). Overtreatment was defined as histopathological finding of cervical intraepithelial lesion grade 1 or normal tissue. RESULTS: Among the 254 included patients, the overall overtreatment rate was 12.6%, whereas in women with a grade 2 colposcopy, it was 3.2% and, in women with grade 1 colposcopy, it was 22.0%. Among the considered factors (age, menopause, and grade 1 colposcopy), only a positive association with overtreatment and grade 1 colposcopy emerged (odds ratio = 8.70, 95% CI = 2.95-25.62, p < .001). CONCLUSIONS: See and treat may be appropriate in women older than 25 years with a visible squamocolumnar junction and a high-grade squamous cervical cytology. Patients need to be informed about the higher risk of overtreatment in case of a grade 1 colposcopic impression, which however may still be considered acceptable. Patient's age and menopausal status should not influence the decision to propose a see-and-treat approach.

Ovarian endometriosis and vitamin D serum levels.

AIM: The aim of this study was to assess the vitamin D serum level in women with ovarian endometriosis; specifically, a possible correlation between the dimensions of ovarian endometriomas and vitamin D serum levels was evaluated. MATERIALS AND METHODS: This was an observational study of childbearing-age women diagnosed with singleton ovarian endometrioma from January 2015 to December 2015. Women diagnosed with multiple ovarian endometriomas or extraovarian endometriosis were excluded. RESULTS: Forty-nine women constituted the initial study cohort. In these women, the mean (±SD) 25-OH-D3 serum level was 22.0 (±8.9) ng/ml, and 42 of them (85.7%) were diagnosed with hypovitaminosis D. In the "hypovitaminosis D women", the mean (± SD) diameter of ovarian endometriomas was 40.2 ± 22.6 mm, while in the "normal vitamin D serum level women" it was 26.7 ± 12.1 mm (p = 0.1). However, a significant linear correlation between 25-OH-D3 serum level and the diameter of ovarian endometriomas was found (r = -0.3, p = 0.03). CONCLUSION: We found a relatively high rate of women with ovarian endometriosis and hypovitaminosis D. Interestingly, a significant linear correlation between 25-OH-D3 serum levels and the diameter of ovarian endometrioma emerged.

The association between ultrasound-estimated visceral fat deposition and uterine fibroids: an observational study.

Uterine fibroids are the most common neoplasm of the genital tract in reproductive women. Obesity holds a role as risk factor for uterine fibroids, through hormonal and inflammatory mechanisms. Visceral fat is a hormonally active tissue, so an increase in visceral fat may be considered as a risk factor, through the increased production of inflammatory mediators. The aim of the study was, therefore, to evaluate the association between the presence of uterine fibroids and fat tissue distribution, and to assess the efficacy of both anthropometric and instrumental indicators, in particular the sonographic measurement of preperitoneal fat thickness (PFT) and subcutaneous fat thickness (SFT). Study group consisted of childbearing-age women with at least one uterine fibroid with a diameter ≥10 mm (n = 71), all the childbearing-age women who access to the outpatient service of our institution in the same period, without evidence of uterine fibroids, constituted the control group (n = 145). A significantly difference in BMI (p = 0.0034), PFT (p < 0.0001), and SFT (p = 0.0003) emerged. At the multivariate analysis, only PFT showed an independent significant association with the presence of uterine fibroids (p < 0.0001). The ROC curve analysis identified a cut-off value of 6.7 mm of PFT as discriminator for the presence of uterine fibroids.

Laparoscopic uterine artery bipolar coagulation plus myomectomy vs traditional laparoscopic myomectomy for "large" uterine fibroids: comparison of clinical efficacy.

PURPOSE: Laparoscopic myomectomy is the uterus-preserving surgical approach of choice in case of symptomatic fibroids. However, it can be a difficult procedure even for an experienced surgeon and can result in excessive blood loss, prolonged operating time and postoperative complications. A combined approach with laparoscopic uterine artery occlusion and simultaneous myomectomy was proposed to reduce these complications. The aim of this study was to evaluate the safety and efficacy of the combined laparoscopic approach in women with symptomatic "large" intramural uterine fibroids, compared to the traditional laparoscopic myomectomy alone. METHODS: Prospective nonrandomized case-controlled study of women who underwent a conservative surgery for symptomatic "large" (≥ 5 cm in the largest diameter) intramural uterine fibroids. The "study group" consisted of women who underwent the combined approach (laparoscopic uterine artery bipolar coagulation and simultaneous myomectomy), while women who underwent the traditional laparoscopic myomectomy constituted the "control group". A comparison between the two groups was performed, and several intraoperative and postoperative outcomes were evaluated. RESULTS: No significant difference in the overall duration of surgery between women of the "study group" and "control group" emerged; however, a significantly shorter surgical time for myomectomy was observed in the "study group". The intraoperative blood loss and the postoperative haemoglobin drop were significantly lower in the "study group". No difference in the postoperative pain between groups emerged, and the postoperative hospital stay was similar in the two groups. CONCLUSIONS: The laparoscopic uterine artery bipolar coagulation and simultaneous myomectomy is a safe and effective procedure, even in women with symptomatic "large" intramural uterine fibroids, with the benefit of a significant reduction in the intraoperative blood loss when compared to the traditional laparoscopic myomectomy.

Follow up in women with biopsy diagnosis of cervical low-grade squamous intraepithelial lesion (LSIL): how long should it be?

AIM: To analyse the regression rate and the risk of persistence or progression of the lesions in women with a histopathological diagnosis of cervical low-grade squamous intraepithelial lesion (LSIL). MATERIALS AND METHODS: Retrospective cohort study of women with biopsy diagnosis of cervical LSIL, from January 2010 to December 2013. After the initial diagnosis of LSIL, all the women underwent scheduled follow-up examinations with cytology every 6 months for 2 years and an HPV test after 1 year. RESULTS: At the 24 -month follow-up, the regression of cervical LSIL was observed in 88.5% of the women. 10.8% of the women had a persistent lesion, while a progression towards cervical HSIL was reported in 0.7% of the women. The risk of persistence or progression of histological LSIL was higher in women with ASC-H or HSIL on the referral cytology and in tobacco users. CONCLUSION: In women with biopsy diagnosis of cervical LSIL, preceded by ASCUS or LSIL on cytology, a high rate of regression was observed and, in most of the cases, the regression occurred in the first year of follow-up. In women with cervical LSIL, preceded by ASC-H or HSIL on cytology, and in tobacco users, a higher risk of persistence and progression was observed. Thus, in these cases, repeated follow-up examinations, even with the HR-HPV test, are advisable.