Recent Advances in Endometrial Cancer Prevention, Early Diagnosis and Treatment.

Endometrial cancer is the sixth commonest cancer in women worldwide, with over 417,000 diagnoses in 2020. The disease incidence has increased by 132% over the last 30 years and is set to continue to rise in response to an ageing population and increasing global rates of obesity and diabetes. A greater understanding of the mechanisms driving endometrial carcinogenesis has led to the identification of potential strategies for primary disease prevention, although prospective evaluation of their efficacy within clinical trials is still awaited. The early diagnosis of endometrial cancer is associated with improved survival, but has historically relied on invasive endometrial sampling. New, minimally invasive tests using protein and DNA biomarkers and cytology have the potential to transform diagnostic pathways and to allow for the surveillance of high-risk populations. The molecular classification of endometrial cancers has been shown to not only have a prognostic impact, but also to have therapeutic value and is increasingly used to guide adjuvant treatment decisions. Advanced and recurrent disease management has also been revolutionised by increasing the use of debulking surgery and targeted treatments, particularly immunotherapy. This review summarises the recent advances in the prevention, diagnosis and treatment of endometrial cancer and seeks to identify areas for future research.

FARGO-360: a multi-disciplinary survey of practice and perspectives on provision of care for patients with frailty presenting with gynecological cancers in the UK and Ireland.

OBJECTIVES: Frailty has been associated with worse cancer-related outcomes for people with gynecological cancers. However, the lack of clear guidance on how to assess and modify frailty prior to instigating active treatments has the potential to lead to large variations in practice and outcomes. This study aimed to evaluate current practice and perspectives of healthcare practitioners on the provision of care for patients with frailty and a gynecological cancer. METHODS: Data were collected via a questionnaire-based survey distributed by the Audit and Research in Gynecological Oncology (ARGO) collaborative to healthcare professionals who identified as working with patients with gynecological malignancies in the United Kingdom (UK) or Ireland. Study data were collected using REDCap software hosted at the University of Manchester. Responses were collected over a 16 week period between January and April 2021. RESULTS: A total of 206 healthcare professionals (30 anesthetists (14.6%), 30 pre-operative nurses (14.6%), 51 surgeons (24.8%), 34 cancer specialist nurses (16.5%), 21 medical/clinical oncologists (10.2%), 25 physiotherapists/occupational therapists (12.1%) and 15 dieticians (7.3%)) completed the survey. The respondents worked at 19 hospital trusts across the UK and Ireland. Frailty scoring was not routinely performed in 63% of care settings, yet the majority of practitioners reported modifying their practice when providing and deciding on care for patients with frailty. Only 16% of organizations surveyed had a dedicated pathway for assessment and management of patients with frailty. A total of 37% of respondents reported access to prehabilitation services, 79% to enhanced recovery, and 27% to community rehabilitation teams. CONCLUSION: Practitioners from all groups surveyed considered that appropriate training, dedicated pathways for optimization, frailty specific performance indicators and evidence that frailty scoring had an impact on clinical outcomes and patient experience could all help to improve care for frail patients.

Pathogenesis of Vertebral Anterior Wedge Deformity: A 2-Stage Process?

STUDY DESIGN: Biomechanical and radiographical study on cadaveric spines. OBJECTIVE: To explain the pathogenesis of vertebral "anterior wedge" deformity, which causes senile kyphosis. SUMMARY OF BACKGROUND DATA: This deformity arises with minimal trauma and is difficult to reproduce in cadaveric spines. We hypothesize that wedging is created by a 2-stage process. First, excessive loading damages a vertebral endplate and decompresses the adjacent intervertebral disc. This alters load sharing between the vertebral body cortex and trabeculae so that subsequent cyclic loading causes progressive collapse of the unsupported anterior cortex. METHODS: Thirty-four cadaveric thoracolumbar "motion segments," aged 70 to 98 years, were positioned in flexion and overloaded in compression. Physiologically reasonable cyclic compressive loading was then applied to each flexed specimen, at progressively higher loads, for up to 2 hours. Before and after initial overload and again after cyclic loading, the distribution of loading on the vertebra was assessed from measurements of compressive stress within the adjacent disc. These "stress profiles" were repeated in the neutral, flexed, and extended postures. Progressive vertebral body deformity was assessed radiographically. RESULTS: Compressive overload induced endplate fracture at an average force of 2.31 kN. There was minimal anterior wedging, but pressure in the adjacent disc nucleus (in flexion) fell by an average of 55% and neural arch load bearing increased by 166%. Subsequent cyclic loading exaggerated these changes and concentrated compressive stress within the anterior annulus. After both stages, height of the anterior and posterior vertebral cortexes was reduced by 32% and 12%, respectively, so that anterior wedging of the vertebral body increased from 5.0° to 11.4° on average. All changes were highly significant (P < 0.001). CONCLUSION: Anterior wedge deformities can be created consistently by a 2-stage process involving initial endplate damage, followed by progressive collapse of the anterior cortex. Detecting initial endplate damage may be important to minimize vertebral deformity in patients with osteoporosis. LEVEL OF EVIDENCE: N/A.

Is kyphoplasty better than vertebroplasty at restoring form and function after severe vertebral wedge fractures?

BACKGROUND CONTEXT: The vertebral augmentation procedures, vertebroplasty and kyphoplasty, can relieve pain and facilitate mobilization of patients with osteoporotic vertebral fractures. Kyphoplasty also aims to restore vertebral body height before cement injection and so may be advantageous for more severe fractures. PURPOSE: The purpose of this study was to compare the ability of vertebroplasty and kyphoplasty to restore vertebral height, shape, and mechanical function after severe vertebral wedge fractures. STUDY DESIGN/SETTING: This is a biomechanical and radiographic study using human cadaveric spines. METHODS: Seventeen pairs of thoracolumbar "motion segments" from cadavers aged 70-98 years were injured, in a two-stage process involving flexion and compression, to create severe anterior wedge fractures. One of each pair underwent vertebroplasty and the other kyphoplasty. Specimens were then compressed at 1 kN for 1 hour to allow consolidation. Radiographs were taken before and after injury, after treatment, and after consolidation. At these same time points, motion segment compressive stiffness was assessed, and intervertebral disc "stress profiles" were obtained to characterize the distribution of compressive stress on the vertebral body and neural arch. RESULTS: On average, injury reduced anterior vertebral body height by 34%, increased its anterior wedge angle from 5.0° to 11.4°, reduced intradiscal (nucleus) pressure and motion segment stiffness by 96% and 44%, respectively, and increased neural arch load bearing by 57%. Kyphoplasty caused 97% of the anterior height loss to be regained immediately, although this reduced to 79% after consolidation. Equivalent gains after vertebroplasty were significantly lower: 59% and 47%, respectively (p<.001). Kyphoplasty reduced vertebral wedging more than vertebroplasty (p<.02). Intradiscal pressure, neural arch load bearing, and motion segment compressive stiffness were restored significantly toward prefracture values after both augmentation procedures, even after consolidation, but these mechanical effects were similar for kyphoplasty and vertebroplasty. CONCLUSIONS: After severe vertebral wedge fractures, vertebroplasty and kyphoplasty were equally effective in restoring mechanical function. However, kyphoplasty was better able to restore vertebral height and reverse wedge deformity.