Background: Clinical reasoning is a key ability essential for practising health professionals. However, little is known about the current global adoption of clinical reasoning teaching and assessment. Purpose: We aimed to provide insights into how clinical reasoning is deliberately taught and assessed in curricula worldwide and to identify needs and perceived barriers for teaching clinical reasoning to students and educators. Methods: A questionnaire was devised by an international expert group and distributed in a large international medical education community. Data were collected in 2018 and analysed using descriptive statistics. We identified themes in free-text responses using content analysis. Results: Three hundred and thirteen responses from 76 countries were collected. Most respondents were from Europe (34%). While the presence of a longitudinal clinical reasoning curriculum was only reported by 28%, 85% stated that such a curriculum was needed. The lack of awareness of the need to explicitly teach clinical reasoning was the most commonly identified barrier. For assessment, the greatest need identified was for more workplace-based assessment. Conclusions: Global respondents indicate the need to implement explicit longitudinal clinical reasoning curricula. Our findings suggest that efforts should be put into improving faculty development, including evidence-based materials on how to teach and assess clinical reasoning.

Endometrial cancer (EC) is the most common gynaecologic malignancy in the developed countries. Recent evidence suggests that histopathological subtyping together with molecular subgrouping can lead to more accurate assessment of the risk profile for the patient. Clinical studies suggest the currently used molecular classification improves the risk assessment of women with endometrial cancer but does not explain the differences in recurrence profiles clearly. This could be improved by novel markers. One of such are mutations in the β-catenin (CTNNB1) gene, a frequently mutated gene in endometrial cancer. This shows mutations mostly at phosphorylation sites of the β-catenin and almost exclusively in the endometrial subgroup of no specific molecular profile. CTNNB1 mutations lead to alterations in the Wnt/β-catenin signalling pathway, involved in the carcinogenesis and progression of EC by inducing transcription of target genes, whose function is to regulate the cell cycle. Although tumours with mutations in CTNNB1 tend to have low-risk characteristics, they are related to worse outcomes with significantly increased rate of disease recurrence and lower overall survival.

Background: Gestational trophoblastic disease (GTD) is a heterogeneous group of rare tumours characterised by abnormal proliferation of trophoblastic tissue. It consists of benign or premalignant conditions, such as complete and partial molar pregnancy and variants of malignant diseases. The malignant tumours specifically are commonly referred to as gestational trophoblastic neoplasia (GTN). They consist of invasive mole, choriocarcinoma, placental-site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT). Conclusions: Patients with GTD are often asymptomatic, although vaginal bleeding is a common presenting symptom. With the advances in ultrasound imaging in early pregnancy, the diagnosis of molar pregnancy is most commonly made in the first trimester of pregnancy. Sometimes, additional imaging such as chest X-ray, CT or MRI can help detect metastatic disease. Most women can be cured, and their reproductive function can be preserved. In this review, we focus on the advances in management strategies for gestational trophoblastic disease as well as possible future research directions.

We present findings of a cancer multidisciplinary-team (MDT) coordinated mainstreaming pathway of unselected 5-panel germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 and parallel somatic BRCA1/BRCA2 testing in all women with epithelial-OC and highlight the discordance between germline and somatic testing strategies across two cancer centres. Patients were counselled and consented by a cancer MDT member. The uptake of parallel multi-gene germline and somatic testing was 97.7%. Counselling by clinical-nurse-specialist more frequently needed >1 consultation (53.6% (30/56)) compared to a medical (15.0% (21/137)) or surgical oncologist (15.3% (17/110)) (p < 0.001). The median age was 54 (IQR = 51–62) years in germline pathogenic-variant (PV) versus 61 (IQR = 51–71) in BRCA wild-type (p = 0.001). There was no significant difference in distribution of PVs by ethnicity, stage, surgery timing or resection status. A total of 15.5% germline and 7.8% somatic BRCA1/BRCA2 PVs were identified. A total of 2.3% patients had RAD51C/RAD51D/BRIP1 PVs. A total of 11% germline PVs were large-genomic-rearrangements and missed by somatic testing. A total of 20% germline PVs are missed by somatic first BRCA-testing approach and 55.6% germline PVs missed by family history ascertainment. The somatic testing failure rate is higher (23%) for patients undergoing diagnostic biopsies. Our findings favour a prospective parallel somatic and germline panel testing approach as a clinically efficient strategy to maximise variant identification. UK Genomics test-directory criteria should be expanded to include a panel of OC genes.

Over the past century, numerous methods for assessing cell viability have been developed, and there are many different ways to categorize these methods accordingly. We have chosen to use the Organisation for Economic Co-operation and Development (OECD) classification due to its regulatory importance. The OECD categorizes these methods into four groups: non-invasive cell structure damage, invasive cell structure damage, cell growth, and cellular metabolism. Despite the variety of cell viability methods available, they can all be categorized within these four groups, except for two novel methods based on the cell membrane potential, which we added to the list. Each method operates on different principles and has its own advantages and disadvantages, making it essential for researchers to choose the method that best fits their experimental design. This review aims to assist researchers in making this decision by describing these methods regarding their potential use and providing direct references to the cell viability assessment methods. Additionally, we use the OECD classification to facilitate potential regulatory use and to highlight the need for adding a new category to their list.

Endometrial and cervical cancers are the two most common gynaecological malignancies and among the leading causes of death worldwide. The extracellular matrix (ECM) is an important component of the cellular microenvironment and plays an important role in developing and regulating normal tissues and homeostasis. The pathological dynamics of the ECM contribute to several different processes such as endometriosis, infertility, cancer, and metastasis. Identifying changes in components of ECM is crucial for understanding the mechanisms of cancer development and its progression. We performed a systematic analysis of publications on the topic of changes in the extracellular matrix in cervical and endometrial cancer. The findings of this systematic review show that matrix metalloproteinases (MMP) play an important role impacting tumour growth in both types of cancer. MMPs degrade various specific substrates (collagen, elastin, fibronectin, aggrecan, fibulin, laminin, tenascin, vitronectin, versican, nidogen) and play a crucial role in the basal membrane degradation and ECM components. Similar types of MMPs were found to be increased in both cancers, namely, MMP-1, MMP-2, MMP-9, and MMP-11. Elevated concentrations of MMP-2 and MMP-9 were correlated with the FIGO stage and are associated with poor prognosis in endometrial cancer, whereas in cervical cancer, elevated concentrations of MMP-9 have been associated with a better outcome. Elevated ADAMTS levels were found in cervical cancer tissues. Elevated disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) levels were also found in endometrial cancer, but their role is still unclear. Following these findings, this review reports on tissue inhibitors of ECM enzymes, MMPs, and ADAMTS. The present review demonstrates changes in the extracellular matrix in cervical and endometrial cancers and compared their effect on cancer development, progression, and patient prognosis.