Global changes in bladder cancer mortality in the elderly.

BACKGROUND: Bladder cancer is the 14th most common cause of cancer deaths worldwide and has a mean age of diagnosis of 73 years. Elderly people have fewer curative treatment options for muscle invasive bladder cancer. The aim of this study is to investigate how bladder cancer mortality has changed over the past forty years in different world regions to assess discrepancies between elderly and younger patients with bladder cancer. METHODS: Bladder cancer mortality data were extracted from the World Health Organisation's GLOBOCAN database. Age-standardised mortality rates (ASMR) for bladder cancer were computed by year, sex, region and Human Development Index (HDI) using the world standard population. RESULTS: Overall ASMR in all available countries with data between 1986 and 2014 for men aged ≥ 75 has decreased from 101.2 to 89.9 per 100,000 (-11.2%). The decrease in ASMR for men < 75 has been 0.3-2.0 per 100,000 (-39.4%). In women aged ≥ 75 ASMR has decreased from 26.9 to 22.5 per 100,000 (-16.4%) and in women < 75 the ASMR has decreased from 0.76 to 0.56 per 100,000 (-26.4%). Correlation analysis showed a positive linear relationship between Human Development Index (HDI) and improvement in age-standardised mortality rate in all ages. Pearson's coefficient showed that correlation was strongest in the 60-74 age group (r = -0.61, p < 0.001) and weakest in those aged ≥ 75 (r = -0.39, p = 0.01). CONCLUSION: Bladder cancer mortality is not improving in the elderly at the same rate as the rest of the population. Particular focus should be applied in future research to enhance and expand treatment options for bladder cancer that are appropriate for elderly patients.

Accuracy of the Vesical Imaging-Reporting and Data System (VIRADS) for pre-treatment staging of bladder cancer in an Australian cohort.

INTRODUCTION: To evaluate the performance of the Vesical Imaging-Reporting and Data System (VIRADS) in differentiating muscle-invasive and non-muscle-invasive bladder cancer and whether this reporting system improves inter-reader agreement. METHODS: Sixty-four cases of multiparametric 3 tesla bladder MRI from January 2014 to May 2020 were reviewed retrospectively. T2-weighted, diffusion and post-contrast images were reviewed. All magnetic resonance images were reported by a radiologist with 15 years' experience (Reader 1) and a final year radiology trainee with a special interest in urogenital imaging with 3 years of experience (Reader 2). Both readers were blinded to clinical history and histopathology results when scoring each lesion. RESULTS: The sensitivity and specificity for differentiating MIBC and NMIBC were 91% and 68%, respectively, for Reader 1 and 91% and 63%, respectively, for Reader 2. The inter-reader agreement for assigning VIRADS scores was 0.79. The area under the receiver operator curve for Reader 1 and 2 were not significantly different (Reader 1 = 0.79, Reader 2 = 0.77, P = 0.83). CONCLUSIONS: Staging of bladder cancer prior to treatment can be accurately and reliably diagnosed using VIRADS, a novel, standardised reporting system for bladder MRI.

Molecular mechanism of transglutaminase-2 in corneal epithelial migration and adhesion.

Migration of cells in the ocular surface underpins physiological wound healing as well as many human diseases. Transglutaminase (TG)-2 is a multifunctional cross-linking enzyme involved in the migration of skin fibroblasts and wound healing, however, its functional role in epithelial migration has not been evaluated. This study investigated the importance of TG-2 in a murine corneal wound healing model as well as the mechanistic role of TG-2 in the regulation of related biological processes such as cell adhesion and migration of cultured human corneal epithelial (HCE-T) cells. Corneal wound closure was delayed in homozygous TG-2 deleted mice compared to wild type mice. HCE-T cells that were knocked-down for TG-2 expression through stable expression of a short-hairpin (sh) RNA targeting TG-2, were delayed in closure of scratch wounds (48 compared to 12h in control cells expressing scrambled shRNA). TG-2 knockdown did not influence epithelial cell cycle progression or proliferation, rather, it led to reduced epithelial cell adhesion, spreading and velocity of migration. At the molecular level, TG-2 knockdown reduced phosphorylation of ß-3 integrin at Tyr747, paxillin at Ser178, vinculin at Tyr822 and focal adhesion kinase at Tyr925 simultaneous with reduced activation of Rac and CDC42. Phosphorylation of paxillin at Ser178A has been shown to be indispensable for the migration of corneal epithelial cells (Kimura et al., 2008) [18]. TG-2 dependent ß-3 integrin activation, serine-phosphorylation of paxillin, and Rac and CDC42 activation may thus play a key functional role in enhancing corneal epithelial cell adhesion and migration during wound healing.