New Insights into Endometrial Cancer.

EC is the most common cancer in the female genital tract in developed countries, and with its increasing incidence due to risk factors, such as aging and obesity, tends to become a public health issue. Although EC is a hormone-dependent neoplasm, there are no recommendations for the determination of steroid hormone receptors in the tumor tissue and no hormone therapy has ever been assessed in the adjuvant setting. Furthermore, its immune environment has been slightly characterized, but recent evidences point out how EC microenvironment may increase self-tolerance by reducing the recruitment of cytotoxic immune cells to the tumor site and/or modifying their phenotype, making these cells no longer able to suppress tumor growth. Here we highlight insights for EC management from diagnosis to a desirable trend of personalized treatment.

Asymptomatic SARS-CoV-2 infections in pregnant patients in an Italian city during the complete lockdown.

Data from both New York and London report a high prevalence of the asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnant patients admitted for delivery, raising questions on the possible correlated dangers (ie, contacts with healthcare workers; the possible creation of an intrahospital outbreak at birth; and conflicting evidence on vertical transmission). For this study, results from SARS-CoV-2 screening via nasopharyngeal swab from maternity wards of the four hospitals of Genoa, Italy, were collected during a month of complete lockdown from 1 April to 30 April 2020. Out of 333 tested women, only 9 were symptomatic. Only one symptomatic patient (0.3%) and six asymptomatic ones (1.8%) tested positive. Out of the six positive asymptomatic patients, five were from the most disadvantaged neighborhood of the city (assessed by postal code). In conclusion, even if Italy was badly affected by coronavirus disease 2019 in the studied month, the reported prevalence of SARS-CoV-2 infections in asymptomatic pregnant patients at term was lower than the ones reported in the literature.

Imaging findings of ovarian leiomyosarcoma with histopathologic correlations.

Leiomyosarcoma (LMS) is a malignant mesenchymal tumor deriving from smooth muscle. Ovarian LMS is exceedingly rare and only few reports have been reported in literature. The article illustrates a case of ovarian leiomyosarcoma in a 61-year-old woman, describing CT and MRI features correlated to histopathologic findings. LMS should be included in the differential diagnosis of solid and multiloculated ovarian lesions, in particular in post-menopausal women.

miRNA-Mediated KHSRP Silencing Rewires Distinct Post-transcriptional Programs during TGF-ß-Induced Epithelial-to-Mesenchymal Transition.

Epithelial-to-mesenchymal transition (EMT) confers several traits to cancer cells that are required for malignant progression. Here, we report that miR-27b-3p-mediated silencing of the single-strand RNA binding protein KHSRP is required for transforming growth factor ß (TGF-ß)-induced EMT in mammary gland cells. Sustained KHSRP expression limits TGF-ß-dependent induction of EMT factors and cell migration, whereas its knockdown in untreated cells mimics TGF-ß-induced EMT. Genome-wide sequencing analyses revealed that KHSRP controls (1) levels of mature miR-192-5p, a microRNA that targets a group of EMT factors, and (2) alternative splicing of a cohort of pre-mRNAs related to cell adhesion and motility including Cd44 and Fgfr2. KHSRP belongs to a ribonucleoprotein complex that includes hnRNPA1, and the two proteins cooperate in promoting epithelial-type exon usage of select pre-mRNAs. Thus, TGF-ß-induced KHSRP silencing is central in a pathway leading to gene-expression changes that contribute to the cellular changes linked to EMT.

Diverse roles of the nucleic acid-binding protein KHSRP in cell differentiation and disease.

The single-stranded nucleic acid-binding protein KHSRP (KH-type splicing regulatory protein) modulates RNA life and gene expression at various levels. KHSRP controls important cellular functions as different as proliferation, differentiation, metabolism, and response to infectious agents. We summarize and discuss experimental evidence providing a potential link between changes in KHSRP expression/function and human diseases including neuromuscular disorders, obesity, type II diabetes, and cancer.

Metformin: risk-benefit profile with a focus on cancer.

INTRODUCTION: Epidemiological evidence suggests an increased incidence of cancer in obese, prediabetic, and diabetic patients and a reduced risk of cancer incidence and mortality in diabetic patients on metformin compared with other antidiabetic drugs. In vitro studies support the efficacy of metformin in cancer therapy and prevention. Although metformin seems to be promising as a cancer chemopreventive or therapeutic drug, the principal consideration is whether metformin will be effective in cancer clinical trials for nondiabetic subjects or only in diabetics or subjects with insulin resistance. Safety of metformin is even more important in treating nondiabetic patients. AREAS COVERED: The present review focuses on epidemiological data and clinical trials testing the efficacy of metformin on cancer, the safety in nondiabetic patients and the future development of this promising drug. EXPERT OPINION: Meta-analyses of epidemiological in which metformin treatment has been used for diabetic patients show a positive trend for benefit; nevertheless, clinical data outcomes are preliminary and the results of ongoing trials are awaited. The different types of cancer, heterogeneity of populations and presence of comorbidity make it difficult to determine the benefits of metformin in cancer prevention and treatment.

New approach in vaginal prolapse repair: mini-invasive surgery associated with application of platelet-rich fibrin.

INTRODUCTION AND HYPOTHESIS: Platelet-rich fibrin (PRF) matrix is an autologous leukocyte and PRF biomaterial. PRF is a fibrin matrix polymerized in a tetramolecular structure with the incorporation of platelets, leukocytes, cytokines, and circulating stem cells. The three-dimensional structure of PRF is optimal for migration of endothelial cells and fibroblasts. It permits rapid angiogenesis and easier remodeling of fibrin in a more resistant connective matrix. In vaginal surgery, PRF may act as a graft material with better healing and better functional outcome. METHODS: We performed a prospective observational study on ten consecutive women requiring surgery for prolapse recurrence (stage II or higher). These women had high risks for recurrence, erosion with graft materials, and intraoperative and postoperative complications with traditional pelvic reconstructive surgical procedures. ICS score and P-QoL Questionnaire results were assessed preoperatively and postoperatively. Surgery consisted of anterior, posterior, or apical repair plus PRF. Follow-up was performed at 1, 6, 12, 18, and 24 months. RESULTS: Anatomically, the success rate was 80%. Prolapse symptoms improved by 100%. Sexual activity increased by 20% without dyspareunia. The surgical time was satisfactory (mean, 38.5 min). There were no intraoperative or postoperative complications. CONCLUSIONS: The use of PRF for site-specific prolapse repair is associated with a good functional outcome because of the healing and mechanical properties of PRF.

Hysterectomy and women satisfaction: total versus subtotal technique.

INTRODUCTION: The impact of different surgical procedures on women's satisfaction after hysterectomy is a topical issue. The aim of this study was to investigate the impact of sub-total and total hysterectomy on women's satisfaction, evaluated with questionnaire assessment of sexual activity, body image, and health status. MATERIALS AND METHODS: A prospective, randomized, non-blind study was conducted. In the study period of 3 years, 105 women were enrolled and completed the questionnaires [EuroQol (EQ-5D), body image scale (BIS), sexual activity questionnaire] 2 weeks before and 1 year after surgery. RESULTS: Both total and sub-total hysterectomy resulted with improvements in the women's sexual satisfaction (1 year after surgery), but no statistically significant differences were reached between the two groups. A highly significant difference (P < 0.001) in the perception of the body image between total and sub-total hysterectomy, at 1 year after surgery, was underlined. The health-related quality of life resulted significantly better in the "sub-total hysterectomy" group 1 year after surgery (P < 0.05). CONCLUSION: Considering these results, why should a total hysterectomy be performed, if the women's satisfaction seems to be higher using the sub-total technique? In our opinion, the woman undergoing hysterectomy for benign conditions must be counseled regarding the differences between the two techniques and, when possible, a choice must be offered to the woman.

Endometrial directed biopsy during sonohysterography using the NiGo device: prospective study in women with abnormal uterine bleeding.

OBJECTIVE: To determine the accuracy of sonohysterography (SHG), combined with sonography-guided biopsies that are performed by using the NiGo device, in the diagnosis of endometrial pathologies in women with abnormal uterine bleeding (AUB). DESIGN: Prospective study. SETTING: Outpatient clinic. PATIENT(S): One hundred sixteen women with AUB (55 postmenopausal and 61 premenopausal). INTERVENTION(S): Patients underwent transvaginal sonography and SHG; when an endometrial condition needing a biopsy was diagnosed, the biopsy was performed both by using the NiGo device (ASL 1, Imperia, Italy) and by using Pipelle. MAIN OUTCOME MEASURE(S): Feasibility of SHG and endometrial biopsy by NiGo. RESULT(S): Sonohysterography was successfully performed by using the NiGo device in 87.4% of the cases (92.6% of premenopausal women and 81.5% of postmenopausal women). Seventy-eight (86.7%) women were judged to require endometrial biopsy; the NiGo device allowed obtaining an adequate biopsy for histological evaluation in 74 cases (94.9%). There was no statistically significant difference in efficacy between the NiGo and Pipelle in providing a specimen that was adequate for histological evaluation. Although no significant difference was observed in the histological diagnosis performed on the specimens obtained by the two techniques, NiGo allowed diagnosis of more focal lesions (simple hyperplasia, endometrial polyps, and myomas). CONCLUSION(S): The NiGo device allows an adequate biopsy for histological evaluation to be obtained during SHG in an outpatient setting.

Penetration of prulifloxacin into gynaecological tissues after single and repeated oral administrations.

OBJECTIVE: This study aimed to evaluate the penetration into gynaecological tissues of ulifloxacin, the active metabolite of prulifloxacin, a once-daily fluoroquinolone administered once or in repeated doses. METHODS: This was an open-label, randomised study that included 20 consenting female inpatients (age range 40-65 years) requiring total simple hysterectomy as a result of benign disease. Three groups of patients were enrolled: group A (four patients whose gynaecological tissue samples were used to set up the bioanalytical method); group B (eight patients treated 3 hours before surgery with one 600 mg tablet of prulifloxacin); group C (eight patients treated with prulifloxacin 600 mg once daily for 3 days and undergoing surgery 3 hours after the last dose). Patients to be treated with prulifloxacin were randomly allocated to group B or C. During surgery, samples of blood were collected jointly with healthy tissue removed from the endometrium, proximal fallopian tube, vaginal posterior fornix and portio vaginalis. Ulifloxacin concentrations in plasma and gynaecological tissues were determined by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) bioanalytical method. An intrastudy assessment of the bioanalytical method performance was also conducted for plasma and tissues using calibration and quality control data (spiked samples). RESULTS: Ulifloxacin mean concentrations were always higher in group C than in group B patients, both in plasma (0.76 vs 0.53 microg/mL) and in gynaecological tissues, namely fallopian tube (1.38 vs 0.81 microg/g), posterior fornix (1.48 vs 1.05 microg/g), portio vaginalis (1.46 vs 1.45 microg/g) and endometrium (2.20 vs 1.39 microg/g), as expected after repeated drug administrations. Tissue concentrations observed after repeated administrations were generally higher than the ulifloxacin minimum inhibitory concentrations for pathogens more frequently involved in gynaecological bacterial infections. The mean tissue/plasma ratios ranged between 1.5 and almost 3. CONCLUSION: The results of this study are promising but not fully predictive of clinical or microbiological efficacy for prulifloxacin. There is a need for appropriate clinical trials confirming that prulifloxacin is a useful therapeutic tool in patients with gynaecological bacterial infections.

A new technique to obtain endometrial directed biopsy during sonohysterography: the NiGo device.

The primary goal of the clinical evaluation of abnormal uterine bleeding is to establish a specific diagnosis in the most efficient and least invasive manner possible. Hysteroscopy (HS) allows physicians to obtain directed biopsy in addition to direct visualization of the uterine cavity and lesions, but often requires ambulatory surgery centers and some anesthesia, or can potentially result in significant patient discomfort. Sonohysterography (SHG) is less invasive than HS but does not allow a histologic sample. A new technique, called the Nicoletti-Gorlero (NiGo) device, was developed and evaluated to obtain histologic results during SHG. This study is a prospective, observational evaluation between the NiGo device technique and standard HS to obtain endometrial samples. The NiGo device was used to obtain an endometrial sample during SHG in 18 women. In a subsequent session, HS was performed to verify the results. From January 2005 through November 2005 both procedures (SHG + biopsy and HS) were performed on 18 patients. The SHG procedures using the NiGo forcep were performed successfully on 15 out of 18 women, and the endometrial sample was obtained in 14 out of 15 patients. In one patient, the endometrial biopsy obtained provided too little tissue to accomplish histologic evaluation. All 13 pathologic results obtained with the NiGo device were identical with those subsequently obtained with HS. The office-based HS procedure was not successful in two women; in these women, an HS procedure performed in the operating room was necessary. The NiGo device technique allows the physician to obtain sonographic-guided biopsies of the entire endometrium during SHG. The technique is less invasive compared with HS. In our small series, there were no complications during the procedure.

The association between p53 expression, stage and histological features in endometrial cancer.

OBJECTIVE: Alterations of the p53 gene have been widely suggested to be relevant to the development of endometrial carcinoma. However, contradictory results have been reported when immunohistochemical determination of p53 expression has been correlated with stage and histological features of the tumours. STUDY DESIGN: Pathology findings were reviewed and p53 immunoperoxidase staining was performed in 240 cases of endometrial carcinoma. RESULTS: Uterine papillary serous adenocarcinomas showed significantly higher p53 overexpression than uterine endometrioid adenocarcinomas (100.0% versus 61.0%, p<0.005). p53 overexpression was significantly higher in the secretory variant (85.7%) than in the typical endometrioid carcinoma (60.0%) (p<0.05). p53 expression did not differ between early (stage I) and advanced (stage II-IV) carcinomas. Likewise, no difference was observed in p53 expression among different architectural grades. The incidence of metastasis to lymph nodes was similar in p53 positive (13.7%) and in p53 negative tumours (12.5%). CONCLUSION: In the present series, p53 immunostaining did not differ between cases with different FIGO stages or histologic characteristics of the tumours. No simple relationship exists between the immunohistochemical determination of p53 expression and the biological aggressiveness of endometrial carcinomas.

Hysterosalpingography with gadolinium.

We report a case of diagnostic hysterosalpingography performed using gadoteric acid (1,350 mOsm) in a patient with a prior severe generalized adverse reaction to iodinated contrast media.