The Management of Orbital Roof Fractures and Defects: A Review.

PURPOSE: To explore the anatomy, etiopathogenesis, diagnosis and classification, current evidence on intervention and the surgical management of orbital roof fractures and defects (ORFD) for oculoplastic surgeons presented with such cases. METHODS: A review of the current literature through the MEDLINE database using the following search terms: "orbital roof fracture (+treatment/management)," "orbital roof defect (+treatment/management)," "orbital roof erosion (+treatment/management)," "orbital roof repair," "orbital roof," "orbital fracture," "pediatric orbital roof (defect/fracture/erosion)," "orbital anatomy," and "orbital roof anatomy" was conducted. As relatively little has been published on this topic, inclusion criteria were broad and peer-reviewed articles judged to be of clinical importance, relevant to the aims of this review, were included. Non-English abstracts were also included if relevant. Year of publication was not a strict exclusion criterion, and older articles were judged for their suitability based on clinical importance and relevance to current practice. Additional references were obtained from citations in key articles and recommendations from the coauthors based on their areas of expertise. RESULTS: The etiopathogenesis of ORFD varies. Classification systems have been formulated to guide management decisions and can range from conservative management to complex neurosurgery. Eyelid approaches have also been described. This review provides a summary of the evidence for each and a management framework oculoplastic surgeons can use when presented with ORFD. CONCLUSION: Oculoplastic surgeons can be involved, either alone or as part of a multidisciplinary team, in the management of ORFD, and for some, conduct orbital approach reconstructive surgery.

Inequalities in cancer screening, prevention and service engagement between UK ethnic minority groups.

More people in the UK are living with cancer than ever before. With an increasingly ethnically diverse population, greater emphasis must be placed on understanding factors influencing cancer outcomes. This review seeks to explore UK-specific variations in engagement with cancer services in minority ethnic groups and describe successful interventions. The authors wish to highlight that, despite improvement to engagement and education strategies, inequalities still persist and work to improve cancer outcomes across our communities still needs to be prioritised. There are many reasons why cancer healthcare inequities exist for minority communities, reported on a spectrum ranging from cultural beliefs and awareness, through to racism. Strategies that successfully enhanced engagement included language support; culturally-sensitive reminders; community-based health workers and targeted outreach. Focusing on the diverse city of Leicester the authors describe how healthcare providers, researchers and community champions have worked collectively, delivering targeted community-based strategies to improve awareness and access to cancer services.

An optimised patient-derived explant platform for breast cancer reflects clinical responses to chemotherapy and antibody-directed therapy.

Breast Cancer is the most common cancer among women globally. Despite significant improvements in overall survival, many tumours are refractory to therapy and so novel approaches are required to improve patient outcomes. We have evaluated patient-derived explants (PDEs) as a novel preclinical platform for breast cancer (BC) and implemented cutting-edge digital pathology and multi-immunofluorescent approaches for investigating biomarker changes in both tumour and stromal areas at endpoint. Short-term culture of intact fragments of BCs as PDEs retained an intact immune microenvironment, and tumour architecture was augmented by the inclusion of autologous serum in the culture media. Cell death/proliferation responses to FET chemotherapy in BC-PDEs correlated significantly with BC patient progression-free survival (p = 0.012 and p = 0.0041, respectively) and cell death responses to the HER2 antibody therapy trastuzumab correlated significantly with HER2 status (p = 0.018). These studies show that the PDE platform combined with digital pathology is a robust preclinical approach for informing clinical responses to chemotherapy and antibody-directed therapies in breast cancer. Furthermore, since BC-PDEs retain an intact tumour architecture over the short-term, they facilitate the preclinical testing of anti-cancer agents targeting the tumour microenvironment.

Utility of Circulating Tumor DNA for Detection and Monitoring of Endometrial Cancer Recurrence and Progression.

Despite the increasing incidence of endometrial cancer (EC) worldwide and the poor overall survival of patients who recur, no reliable biomarker exists for detecting and monitoring EC recurrence and progression during routine follow-up. Circulating tumor DNA (ctDNA) is a sensitive method for monitoring cancer activity and stratifying patients that are likely to respond to therapy. As a pilot study, we investigated the utility of ctDNA for detecting and monitoring EC recurrence and progression in 13 patients, using targeted next-generation sequencing (tNGS) and personalized ctDNA assays. Using tNGS, at least one somatic mutation at a variant allele frequency (VAF) > 20% was detected in 69% (9/13) of patient tumors. The four patients with no detectable tumor mutations at >20% VAF were whole exome sequenced, with all four harboring mutations in genes not analyzed by tNGS. Analysis of matched and longitudinal plasma DNA revealed earlier detection of EC recurrence and progression and dynamic kinetics of ctDNA levels reflecting treatment response. We also detected acquired high microsatellite instability (MSI-H) in ctDNA from one patient whose primary tumor was MSI stable. Our study suggests that ctDNA analysis could become a useful biomarker for early detection and monitoring of EC recurrence. However, further research is needed to confirm these findings and to explore their potential implications for patient management.

Uncontrollable haemorrhage following dabigatran prophylaxis.

An 88-year-old man, on dabigatran anticoagulation after a total hip replacement 1 week before admission, presented with acute abdominal pain associated with malaena and haematemesis. After examination and investigation, he was found to have a perforated viscus and underwent laparotomy. The perforation was surgically repaired, but the patient suffered from a massive haemorrhage during the operation, requiring intensive care admission postoperatively. The patient subsequently deteriorated despite aggressive treatment and died several days later.