Bladder cancer is the sixth most common cancer in humans. This heterogeneous set of lesions including urothelial carcinoma (Uca) and squamous cell carcinoma (SCC) arise from the urothelium, a stratified epithelium composed of K5-expressing basal cells, intermediate cells and umbrella cells. Superficial Uca lesions are morphologically distinct and exhibit different clinical behaviours: carcinoma in situ (CIS) is a flat aggressive lesion, whereas papillary carcinomas are generally low-grade and non-invasive. Whether these distinct characteristics reflect different cell types of origin is unknown. Here we show using lineage tracing in a murine model of carcinogenesis that intermediate cells give rise primarily to papillary lesions, whereas K5-basal cells are likely progenitors of CIS, muscle-invasive lesions and SCC depending on the genetic background. Our results provide a cellular and genetic basis for the diversity in bladder cancer lesions and provide a possible explanation for their clinical and morphological differences.

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These findings could have important implications for our understanding of cancer tumorigenesis and could move the fields of regeneration and reconstruction forward.

Previous studies have shown that postcall-related fatigue is associated with decreased surgical skills in the operative room. We demonstrate this effect by having residents test their skills, precall and postcall, using a novel easily reproducible technique. Time to complete the three measures analyzed was significantly increased following a 24-hour call for all participants. Fatigue acts as an equalizer of abilities in that the effects of fatigue nullify the benefits of having previous robotic simulator experience.

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