Modern paradigms for prostate cancer detection and management.

Early detection and management of prostate cancer has evolved over the past decade, with a focus now on harm minimisation and reducing overdiagnosis and overtreatment, given the proven improvements in survival from randomised controlled trials. Multiparametric magnetic resonance imaging (mpMRI) is now an important aspect of the diagnostic pathway in prostate cancer, improving the detection of clinically significant prostate cancer, enabling accurate localisation of appropriate sites to biopsy, and reducing unnecessary biopsies in most patients with normal magnetic resonance imaging scans. Biopsies are now performed transperineally, substantially reducing the risk of post-procedure sepsis. Australian-led research has shown that prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has superior accuracy in the staging of prostate cancer than conventional imaging (CT and whole-body bone scan). Localised prostate cancer that is low risk (International Society for Urological Pathology [ISUP] grade 1, Gleason score 3 + 3 = 6; and ISUP grade group 2, Gleason score 3 + 4 = 7 with less than 10% pattern 4) can be offered active surveillance, reducing harms from overtreatment. Prostatectomy and definitive radiation remain the gold standard for localised intermediate and high risk disease. However, focal therapy is an emerging experimental treatment modality in Australia in carefully selected patients. The management of advanced prostate cancer treatment has evolved to now include several novel agents both in the metastatic hormone-sensitive and castration-resistant disease settings. Multimodal therapy with androgen deprivation therapy, additional systemic therapy and radiotherapy are often recommended. PSMA-based radioligand therapy has emerged as a treatment option for metastatic castration-resistant prostate cancer and is currently being evaluated in earlier disease states.

Age-dependent physiological changes, medicines and sex-influenced types of falls.

Background/Study context: We investigated various parameters related to falls including age-dependent physiological changes, regular medicine use and different types of falls experienced. There is a lack of research investigating the impact of health status, sex, polypharmacy and ageing on different types of falls such as unspecified fall on the same level, mechanical fall on the same level relating to slipping, tripping or loosing balance, fall from a chair, vehicle and fall as a result of syncope, fall from steps or stairs and fall from the height. METHODS: The study included a random sample of 250 older patients, which comprised 10% of the total number of patients (n = 2,492), admitted to a large-scale academic hospital following a fall. Patients' medicine and illness history, types of falls, liver, renal and sensory function were collected. Univariate analysis was used to examine associations between the type of fall and explanatory variables, followed by multinominal logistic regression analysis. RESULTS: There was a significant association between the type of fall and sex, p = 0.01, and between the type of fall and regular medicine use, p = 0.002. The multinominal logistic regression analysis revealed that the full model, which considered all explanatory variables together, was statistically significant, p < 0.001. The strongest predictor of all types of falls except 'fall from the height' was female sex followed by the regular medicine use. CONCLUSION: This study identified predictors for various types of falls in older people; the strongest predictor being a female sex followed by regular medicine use. Based on these findings, the medicine prescribing practice in this older population must be carefully reviewed.

Robotic-assisted radical prostatectomy: learning curves and outcomes from an Australian perspective.

Background: Robot-assisted radical prostatectomy (RARP) has been a treatment for men who suffer from intermediated to high-risk prostate cancer in Australia since 2003. The primary outcomes in relation to learning curves in robotic surgery have been extensively researched in overseas populations, but there is no study from a cohort of Australian surgeons performing RARP. This study aims to highlight the effect of RARP learning curves on primary surgical outcomes in a high-volume Australian centre. Methods: A retrospective audit of all RARP performed at Epworth Healthcare from 2016 to 2021 was performed. The primary outcome data collected included operating time (OT), estimated blood loss (EBL), and positive surgical margins (PSM). Exclusion criteria were applied. Positive outcomes were set at OT 240 min, blood loss 310 mL, and negative surgical margins. Results: A total of 3969 cases were analysed for a cohort of 53 surgeons. Of these surgeons, 24 surgeons have performed >50 operations to be able to undergo learning curve analysis. The median OT was 229 min, the median blood loss was 353 mL, and most cases had negative surgical margins (>1 mm, n = 3681, 92.7%). The mean learning curve transition point was 65 cases. There was a significant difference in the EBL and rate of PSM for the higher volume cohort (p = 0.002 and <0.0001, respectively). Conclusion: We perform a retrospective study of all RARP performed at a high-volume Australian centre. Higher volume surgeons demonstrate that primary outcomes improve with a higher caseload (EBL, PSM). Learning curve transition points for RARP are comparable to international high-volume surgeons. Learning curve data could form the benchmark for RARP training and skills development.

Active surveillance versus nonradical treatment for low-risk men with prostate cancer: a review.

Low-risk prostate cancer has traditionally seen a preference towards avoiding treatment-related harms with active surveillance (AS) and multimodal monitoring protocols utilized to assess for disease progression. Large trials have shown variations in mortality and cancer survival benefit between AS and radical treatment, which has prompted further trials into the management of low-risk disease. Nonradical treatments for men on AS have been an emerging field and yet to enter mainstream guidelines or practice. These include pharmacological treatments, focal therapy, nutraceuticals, immunotherapy, and exercise. We present a review of all current major randomized clinical trials for nonradical treatment of men on AS and summarize their findings.

Importance of post-translational modifications on the function of key haemostatic proteins.

Post-translational modifications (PTMs) such as glycosylation and phosphorylation play an important role on the function of haemostatic proteins and are critical in the setting of disease. Such secondary level changes to haemostatic proteins have wide ranging effects on their ability to interact with other proteins. This review aimed to summarize the knowledge of the common PTMs associated with haemostatic proteins and the implications of such modifications on protein function. Haemostatic proteins that represent the main focus for studies specific to PTMs are von Willebrand factor, tissue factor, factor VIII, antithrombin and fibrinogen. These proteins are susceptible to PTMs by glycosylation, phosphorylation, sulphation, citrullination and nitration, respectively, with a significant impact on their function. During synthesis, vWF must undergo extensive PTMs, with N-linked glycosylation being the most common. Increased phosphorylation of tissue factor results in increased affinity for platelets to the vessel endothelium. Citrullination of antithrombin leads to an increased anticoagulant function of this protein and therefore an anticoagulant state that inhibits clot formation. On the contrary, nitration of fibrinogen has been shown to result in a prothrombotic state, whilst sulphation is required for the normal function of Factor VIII. From this review, it is evident that PTMs of haemostatic proteins as a change in protein structure at a secondary level greatly influences the behaviour of the protein at a tertiary level.