Ultrasonography reappraisal of tubal patency in assisted reproduction technology patients: comparison between 2D and 3D-sonohysterosalpingography. A pilot study.

BACKGROUND: The aim of this study was to compare 2D and 3D-sonohysterosalpingography (2D-3D-HyFoSy) with previous diagnostic laparoscopy in the diagnosis of tubal patency, and compare each procedure in terms of procedure's time, perceived pain and complication rate. METHODS: We prospectively recruited infertile women, previously submitted to laparoscopy and randomly allocated into 2D-HyFoSy (group I) and 3D-HyFoSy (group II). We analyzed the results in term of sensitivity, specificity, positive predictive value and negative predictive value in tubal patency evaluation of both procedures in comparison with laparoscopy. RESULTS: We enrolled 50 women, 25 in group I and 25 in group II. 2D-HyFoSy findings obtained in group I, were concordant with laparoscopy in 81% of cases, with a sensitivity of 80% and a specificity of 92%. In group II, a correspondence was present in 88% of examinations, with a sensitivity and specificity of 98% and 91.4% respectively. 3D-HyFoSy was found to be faster and less painful than 2D (P<0.001). CONCLUSIONS: In the diagnosis of tubal occlusion, in the high-risk population, it seems advisable to us using the 3D-HyFoSy as the first-level examination, while, in low-risk patients, if the tubes appear obstructed in 2D-HyFoSy, the 3D-HyFoSy should be indicated before submitting patients to operative laparoscopy.

HPV-related vulvar diseases and perspectives of p16INK4a immunochemistry: a review of the literature.

INTRODUCTION: Two different types of vulvar intraepithelial neoplasia (VIN), HPV-related and HPV-unrelated, should be considered as two separate entities with different management options. The incidence of HPV-related VIN is increasing worldwide and is implicated in carcinogenesis. Our objective is to investigate the use of p16INK4a immunostaining or p16INK4a/p53 double staining for the detection of HPV-related disease to overcome the problem that histological criteria often have significant overlap. METHODS: A systematic literature search was carried out in the online databases PubMed, EMBASE, Cochrane Library, Clincaltrials.gov and Scopus. The key search terms were HPV, VIN, p16INK4a immunochemistry and p53. RESULTS: We found that nuclear and cytoplasmic immunostaining for p16INK4a was intense and diffuse in HPV-associated lesions and weak and focal in normal vulvar epithelium, nondysplastic lesions, lichen sclerosus and keratinizing vulvar squamous cell carcinoma. p53 nuclear immunostaining was always negative in HPV-related disease. CONCLUSIONS: Our findings indicated that p16INK4a or p16INK4a/p53 immunoreactivity, along with histological diagnosis, could be a convenient means to adequately classify VIN and its connection to HPV infection. Therefore, the clear recognition of HPV-associated VIN would lead to an appropriate strategy of treatment and follow-up.

Management of HPV-related cervical disease: role of p16INK4a immunochemistry. Review of the literature.

This systematic review of 43 studies aims to evaluate the absolute and relative sensitivity and specificity of p16INK4a with regard to uterine cervix lesions, describing innovations and techniques for the detection of high-grade cervical dysplasia and allowing correct treatment. Studies were identified in the PubMed database up to March 2015. The keywords hrHPV, p16INK4a gene, and uterine cervical disease (MeSH terms) were used. Only English-language articles were included. We considered retrospective and prospective studies that assessed p16INK4a or p16INK4a/Ki67 staining, with or without HPV-DNA testing (HC2/PCR) as a comparator test, in cytological/histological specimens for which the diagnosis of ASCUS, LSIL or HSIL was verified with a reference standard. The primary outcome for cervical lesions was evaluation of the absolute p16INK4a immunoreactivity; the secondary outcome was evaluation of the relative p16INK4a immunoreactivity versus HPV testing in those studies where comparator tests were available. p16INK4a was more specific than HPV-DNA test (median values of 56.1% vs. 52.25% in CIN grade ≥2 lesions; 82.5% vs. 53% in negative and CIN grade ≥1 lesions). The main limitation of this study is linked to both qualitative and quantitative p16INK4a levels of expression, while the second limitation is the lack of standardized scales. p16INK4a and HPV-DNA used together increased the sensitivity and negative predictive value for CIN detection. p16INK4a can be considered a biomarker of CIN2 or CIN3, indicating a high risk of relapse or evolution to invasive carcinoma. Also p16INK4a-negative CIN should be considered and further research should be performed.

Advances in anti-angiogenic agents for ovarian cancer treatment: The role of trebananib (AMG 386).

Ovarian cancer is a multifaceted and genomically complex disease and has emerged as leading cause of death among gynecological malignancies. Gold-standard treatment consisted of cytoreductive surgery and paclitaxel-carboplatin chemotherapy. Recently, promising results of randomized trials have definitively confirmed the importance of angiogenesis in oncogenesis and ovarian cancer behavior, by showing a significant prolongation of progression-free survival with the addiction of an angiogenesis inhibitor to standard treatment in the first and second line setting. Research over the years has sequentially provided a rapidly broadening signaling landscape and many drugs targeting different signaling pathways of angiogenesis have been developed and investigated. Recently accumulating scientific evidence has started to shed light on the efficacy of AMG 386, a new peptibody reported to neutralize the interaction between angiopoietins (Ang1/2) and their Tie2 receptors, thus representing a promising alternative, both in terms of efficacy and toxicity profile and is considerably under investigation. The aim of this review is to summarize the recent researches and clinical progresses of AMG 386 as a novel target agent in ovarian cancer.