Current and Emerging Strategies for Tubo-Ovarian Cancer Diagnostics.

Tubo-ovarian cancer is the most lethal gynaecological cancer. More than 75% of patients are diagnosed at an advanced stage, which is associated with poorer overall survival. Symptoms at presentation are vague and non-specific, contributing to late diagnosis. Multimodal risk models have improved the diagnostic accuracy of adnexal mass assessment based on patient risk factors, coupled with findings on imaging and serum-based biomarker tests. Newly developed ultrasonographic assessment algorithms have standardised documentation and enable stratification of care between local hospitals and cancer centres. So far, no screening test has proven to reduce ovarian cancer mortality in the general population. This review is an update on the evidence behind ovarian cancer diagnostic strategies.

Pulmonary benign metastasizing uterine leiomyoma (PBML): a case report and review of the literature.

Benign metastasizing leiomyoma (BML) is a rare disorder characterized by the presence of benign smooth muscle tumours in extrauterine sites, typically the lungs. It classically involves perimenopausal women with a history of uterine surgery. The condition follows an indolent course but may cause clinical symptoms with large or widespread lesions. Case presentation: The authors report the case of a 47-year-old female who presented with a 6-month history of irregular vaginal bleeding and severe hot flushes. The patient had no previous history of gynaecological surgery. Ultrasonography and subsequent MRI identified a suspicious 105×65 mm mass involving the right uterine cornu and broad ligament. Computed tomography identified bilateral lung nodules, suspicious for metastases. Histological assessment of the final uterine surgical specimen identified a benign dissecting leiomyoma involving the broad ligament and cervix. BML was diagnosed after thoracoscopic resection of a lung lesion which revealed a histologically identical tumour with entrapped normal lung alveoli. Clinical discussion: This case shows that there is a minority of patients without previous uterine surgery who still go on to develop pulmonary BML. In our case, a combined treatment approach was adopted, involving substitution of hormone replacement therapy to a non-hormonal alternative, thoracoscopic resection of lung lesions and interval surveillance imaging of the chest. Conclusions: BML is a rare condition but should be considered as a differential in women with pulmonary nodules and a history of uterine leiomyomata. Its diagnosis and subsequent counselling can be challenging; therefore cases should be treated by multidisciplinary teams in tertiary specialized centres.

A review of the pathophysiology and evidence-based management of varicoceles and pelvic congestion syndrome.

Pelvic congestion syndrome (PCS) in females and varicoceles in males may be regarded as closely related conditions since the main pathophysiological cause for both processes is pelvic venous insufficiency. Varicoceles are more prevalent amongst sub-fertile males, with an approximate incidence of 15% in the general male population. PCS is commonly diagnosed amongst premenopausal multiparous women, representing one of the leading causes of chronic pelvic pain. Both conditions appear to be predominantly left-sided and are associated with oxidative stress and pro-inflammatory cascades with subsequent effects on fertility. Clinical examination and pelvic ultrasonography play an essential role in the assessment of varicoceles, PCS and chronic pelvic pain. Venography is generally considered as a gold-standard procedure for both conditions. There is still much debate on how these conditions should be managed. This review article provides a comparative analysis of the underlying pathophysiological mechanisms of both PCS and varicoceles, their impact on fertility, as well as their clinical management.

GYNOCARE Update: Modern Strategies to Improve Diagnosis and Treatment of Rare Gynecologic Tumors­Current Challenges and Future Directions

More than 50% of all gynecologic tumors can be classified as rare (defined as an incidence of ≤6 per 100,000 women) and usually have a poor prognosis owing to delayed diagnosis and treatment. In contrast to almost all other common solid tumors, the treatment of rare gynecologic tumors (RGT) is often based on expert opinion, retrospective studies, or extrapolation from other tumor sites with similar histology, leading to difficulty in developing guidelines for clinical practice. Currently, gynecologic cancer research, due to distinct scientific and technological challenges, is lagging behind. Moreover, the overall efforts for addressing these challenges are fragmented across different European countries and indeed, worldwide. The GYNOCARE, COST Action CA18117 (European Network for Gynecological Rare Cancer Research) programme aims to address these challenges through the creation of a unique network between key stakeholders covering distinct domains from concept to cure: basic research on RGT, biobanking, bridging with industry, and setting up the legal and regulatory requirements for international innovative clinical trials. On this basis, members of this COST Action, (Working Group 1, "Basic and Translational Research on Rare Gynecological Cancer") have decided to focus their future efforts on the development of new approaches to improve the diagnosis and treatment of RGT. Here, we provide a brief overview of the current state-of-the-art and describe the goals of this COST Action and its future challenges with the aim to stimulate discussion and promote synergy across scientists engaged in the fight against this rare cancer worldwide.

MiRNA influences in mesenchymal stem cell commitment to neuroblast lineage development.

Mesenchymal Stem Cells (MSCs) are widely used in therapeutic applications. Their plasticity and predisposition to differentiate into a variety of cell types, including those of the neuronal lineage, makes them ideal to study whether a selection of miRNAs may direct the differentiation of MSCs into neuroblasts or neuroblastoma to mature neurons. Following a short-listing, miR-107, 124 and 381 were selected as the most promising candidates for this differentiation. MSCs differentiated into cells of the neural lineage (Conditioned Cells) upon addition of conditioned medium (rich in microvesicles containing miRNAs) obtained from cultured SH-SY5Y neuroblastoma cells. Characterisation of stemness (including SOX2, OCT4, Nanog and HCG) and neural markers (including Nestin, MASH1, TUBB3 and NeuN1) provided insight regarding the neuronal state of each cell type. This was followed by transfection of the three miRNA antagonists and mimics, and quantification of their respective target genes. MiRNA target gene expression following transfection of MSCs with miRNA inhibitors and mimics demonstrated that these three miRNAs were not sufficient to induce differentiation. In conditioned cells the marginal changes in the miRNA target expression levels reflected potential for the modulation of intermediate neural progenitors and immature neuron cell types. Transfection of various combinations of miRNA inhibitors and/or mimics revealed more promise. Undoubtedly, a mix of biomolecules is being released by the SH-SY5Y in culture that induce MSCs to differentiate. Screening for those biomolecules acting synergistically with specific miRNAs will allow further combinatorial testing to elucidate the role of miRNA modulation.

Sentinel Lymph Node Biopsy in the Management of Vulvar Carcinoma: An Evidence-Based Insight.

OBJECTIVE: Lymph node metastasis has been shown to represent the most significant prognostic factor in vulvar carcinoma. Because only 25% to 35% of patients with early stage disease have lymph node metastases, a significant 65% to 75% possibly do not benefit from elective inguinofemoral lymphadenectomy considering the related morbidities of wound infection, breakdown, and lower limb lymphedema. This review article aims to present and summarize the evidence available with regard to sentinel lymph node (SLN)-guided management of vulvar carcinoma. MATERIALS AND METHODS: A literature search was performed in MEDLINE resources using the subject headings "vulvar neoplasms," "sentinel lymph node," "sentinel lymph node biopsy," and "lymphatic metastasis." This search returned 886 articles that were published through January 2017. Prospective studies investigating sentinel node identification techniques and their impact on vulvar cancer management and prognosis were considered. Case reports were excluded from the review. RESULTS: Technetium-99-m-labeled nanocolloid with or without blue dye and more recently indocyanine green fluorescence have been the main techniques used for SLN identification in vulvar carcinoma. Radioisotope and near-infrared techniques have been shown to be superior to blue dye particularly with midline lesions that drain bilaterally or that drain directly to a deep pelvic node. Patients with a small unifocal primary tumor (<4 cm) and no obvious preoperative metastasis have been shown to have low groin recurrence rates and excellent disease-specific survival rates with minimal treatment-related morbidity when undergoing SLN biopsy-guided management. CONCLUSIONS: Sentinel lymph node biopsy-guided management seems to be safe when restricted to International Federation of Gynecology and Obstetrics IB to II cases where tumors are unifocal, less than 4 cm in size, and when there is no evidence of lymph node metastasis on clinical/radiological assessment. This reduces operative morbidity in this cohort of patients.