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BACKGROUND: Bladder cancer is the most expensive cancer to treat on a per-patient basis. Blue light cystoscopy with hexaminolevulinate (BLC) has demonstrated improved diagnostic accuracy compared with white light cystoscopy (WLC) in non-muscle invasive bladder cancer (NMIBC). With higher upfront costs, questions remain about long-term BLC cost outcomes. OBJECTIVE: This study seeks to investigate the 5-year cost comparison of BLC and WLC from the Medicare payer perspective. METHODS: A representative 5-year NMIBC management model was constructed and Medicare reimbursement values were overlaid. The primary outcome was mean year-over-year cumulative cost discounted to present value at a 3% annual percentage rate. The secondary outcome was the rate of clinical events. RESULTS: Patients in the BLC cohort experienced fewer recurrences. On a cumulative present value cost basis, BLC was more expensive per patient in years 1, 2, and 3 than WLC, however, in years 4 and 5, BLC was economically favorable. Year 5 BLC mean cumulative cost savings was $1,172 per patient. Overall, 31.6% of all patients in the BLC group generated cumulative cost savings compared to WLC at year 1 compared with 50.9% at the end of year 5. CONCLUSIONS: Despite a higher initial annual cost, a slight cumulative economic advantage of BLC is realized after surveillance year 3. Additionally, a greater proportion of patients who received BLC achieved cost savings at the end of year 5. As novel technology emerges, economic models can help health care systems predict associated costs and quality improvements.

All living things experience entropy, manifested as a loss of inherited genetic and epigenetic information over time. In yeast, epigenetic changes result in a loss of cell identity and sterility, both hallmarks of yeast aging. In mammals, epigenetic information is also lost over time, but what causes it to be lost and whether it is a cause or a consequence of aging is not known. Using a transgenic mouse system called "ICE" (for Inducible Changes to the Epigenome), we show that the process of repairing non-mutagenic DNA breaks accelerates age-related physiological, cognitive, and molecular changes, including the erosion of the epigenetic landscape, a loss of cellular identity, cellular senescence and advancement of the epigenetic clock. Epigenetic reprogramming through ectopic expression of Oct4, Sox2 and Klf4 (OSK) restores patterns of youthful gene expression. These data support a model in which a loss of epigenetic information is a cause of aging in mammals.

SUMMARYAll living things experience entropy, manifested as a loss of inherited genetic and epigenetic information over time. As budding yeast cells age, epigenetic changes result in a loss of cell identity and sterility, both hallmarks of yeast aging. In mammals, epigenetic information is also lost over time, but what causes it to be lost and whether it is a cause or a consequence of aging is not known. Here we show that the transient induction of genomic instability, in the form of a low number of non-mutagenic DNA breaks, accelerates many of the chromatin and tissue changes seen during aging, including the erosion of the epigenetic landscape, a loss of cellular identity, advancement of the DNA methylation clock and cellular senescence. These data support a model in which a loss of epigenetic information is a cause of aging in mammals.One Sentence SummaryThe act of repairing DNA breaks induces chromatin reorganization and a loss of cell identity that may contribute to mammalian aging