Patients' preferences for the management of non-metastatic prostate cancer: discrete choice experiment

Objective To establish which attributes of conservative treatments for prostate cancer are most important to men. Design Discrete choice experiment. Setting Two London hospitals. Participants 129 men with non-metastatic prostate cancer, mean age 70 years; 69 of 118 (58%) with T stage 1 or 2 cancer at diagnosis. Main outcome measures Men's preferences for, and trade-offs between, the attributes of diarrhoea, hot flushes, ability to maintain an erection, breast swelling or tenderness, physical energy, sex drive, life expectancy, and out of pocket expenses. Results The men's responses to changes in attributes were all statistically significant. When asked to assume a starting life expectancy of five years, the men were willing to make trade-offs between life expectancy and side effects. On average, they were most willing to give up life expectancy to avoid limitations in physical energy (mean three months) and least willing to trade life expectancy to avoid hot flushes (mean 0.6 months to move from a moderate to mild level or from mild to none). Conclusions Men with prostate cancer are willing to participate in a relatively complex exercise that weighs up the advantages and disadvantages of various conservative treatments for their condition. They were willing to trade off some life expectancy to be relieved of the burden of troublesome side effects such as limitations in physical energy

3D Cancer Models: The Need for a Complex Stroma, Compartmentalization and Stiffness

The use of tissue-engineered 3D models of cancer has grown in popularity with recent advances in the field of cancer research. 3D models are inherently more biomimetic compared to 2D cell monolayers cultured on tissue-culture plastic. Nevertheless 3D models still lack the cellular and matrix complexity of native tissues. This review explores different 3D models currently used, outlining their benefits and limitations. Specifically, this review focuses on stiffness and collagen density, compartmentalization, tumor-stroma cell population and extracellular matrix composition. Furthermore, this review explores the methods utilized in different models to directly measure cancer invasion and growth. Of the models evaluated, with PDX and in vivo as a relative "gold standard", tumoroids were deemed as comparable 3D cancer models with a high degree of biomimicry, in terms of stiffness, collagen density and the ability to compartmentalize the tumor and stroma. Future 3D models for different cancer types are proposed in order to improve the biomimicry of cancer models used for studying disease progression

Survival after postoperative morbidity: a longitudinal observational cohort study

Prolonged morbidity after surgery is associated with a risk of premature death for a longer duration than perhaps is commonly thought; however, this risk falls with time. We suggest that prolonged postoperative morbidity measured in this way may be a valid indicator of the quality of surgical healthcare. Our findings reinforce the importance of research and quality improvement initiatives aimed at reducing the duration and severity of postoperative complication

Management of an Elevated PSA and Biopsy Strategies in the Large Prostate

An abnormally high serum PSA is still the most frequent trigger for men to enter a suspected prostate cancer diagnostic pathway. Large prostates, especially the ones with a volume over 100cc, are commonly associated with elevated PSA levels. In men with benign prostatic hyperplasia (BPH), PSA tends to increase over time, something that also occurs in men with untreated progressive prostate cancer. These two factors lead to frequent and unnecessary referrals of men with large prostates to suspected prostate cancer pathways. Many PSA derivatives and risk stratification tools have been developed in an attempt to overcome the limitations of total serum PSA and more accurately predict which men should have prostate biopsies, but translation into routine clinical practice has been hindered. Biopsy strategies may need to be adapted in the setting of a 100cc prostate. Higher sampling density schemes have been advocated for these men to ensure the diagnosis of clinically significant cancer but this can be accompanied by increased side effects. mpMRI is increasingly done prior to biopsy and can aid in the selection of men who can safely avoid biopsies. Likewise, they can help target biopsies to suspicious areas, which may represent a method of balancing adequate sampling of large prostates with adverse events

A novel tissue engineered three-dimensional in vitro colorectal cancer model

The interactions of cancer cells within a solid mass with the surrounding reactive stroma are critical for growth and progression. The surrounding vasculature is recruited into the periphery of the growing tumour to supply cancer cells with nutrients and O2. This study focuses on developing a novel three-dimensional (3-D) in vitro biomimetic colorectal cancer model using colorectal cancer cells and connective tissue cells. The 3-D model comprises a dense artificial cancer mass, created by partial plastic compression of collagen type I containing HT29 colorectal cancer cells, nested in a non-dense collagen type I gel populated by fibroblasts and/or endothelial cells. HT29 cells within the dense mass proliferate slower than when cultured in a two-dimensional system. These cells form tumour spheroids which invade the surrounding matrix, away from the hypoxic conditions in the core of the construct, measured using real time O2 probes. This model is also characterized by the release of vascular endothelial growth factor (VEGF) by HT29 cells, mainly at the invading edge of the artificial cancer mass. This characterization is fundamental in establishing a reproducible, complex model that could be used to advance our understanding of cancer pathology and will facilitate therapeutic drug testing