Primary urothelial carcinoma of the ureter without concurrent renal pelvic or bladder carcinoma: A contemporary clinicopathologic analysis.

Primary urothelial carcinoma (UCa) of the ureter is relatively uncommon, comprising less than 10% of all urinary tract tumors. Typically, ureteral UCa is found in association with other urinary tract tumors, such as renal pelvic or bladder UCa, making it challenging to analyze the clinicopathologic features in isolation. With only a few small case series and case reports available, our understanding of primary ureteral UCa is limited. Herein, we conducted one of the largest studies to date of primary ureteral UCa without concurrent renal pelvic or bladder UCa. Clinicopathologic parameters including extent of invasion, lymphovascular invasion, variant histology, presence of UCa in situ, inverted growth pattern, and clinical follow-up information were obtained. Ninety-seven cases were included in the study. Thirty-nine cases (40%) showed invasion, the preponderance of which invaded lamina propria (15%; 15/97), followed by periureteral soft tissue/adipose (14%; 14/97), muscularis propria (9%; 9/39), and seminal vesicle invasion (1%; 1/97). Clinical follow-up data was available for 80/89 (89%) patients with a mean duration of 35 months (range: 1-206 months). Metastatic UCa developed in 28/89 (35%) patients, 20/28 (71%) of which had invasive disease at presentation. Of the 17 (21%) patients who died, 12 (71%) initially presented with invasive UCa. Although more patients had non-invasive UCa, the propensity for worse outcomes in patients with invasive disease is greater compared to other urinary tract sites. These findings further emphasize the importance of early recognition of these tumors, in view of the relatively high preponderance of advanced disease and mortality in a subset of these patients.

Invasive high-grade urothelial carcinoma of the bladder, renal pelvis, ureter, and prostatic urethra arising in a background of urothelial carcinoma with an inverted growth pattern: a contemporary clinicopathological analysis of 91 cases.

Urothelial carcinoma with an inverted/endophytic growth pattern can occasionally mimic inverted urothelial papilloma and pose diagnostic challenges when assessing the presence or absence of invasion. Making these distinctions is critical for guiding appropriate treatment and improving patient outcomes. Here we conducted one of the largest studies to date of invasive high-grade urothelial carcinoma arising in a background of urothelial carcinoma with an inverted growth pattern. Primary sites examined included bladder, renal pelvis, ureter, and prostatic urethra. Clinicopathological parameters including extent of invasion, variant histology, presence of urothelial carcinoma in situ, and clinical follow-up were obtained. Ninety-one cases from 82 patients were included in the study. Lamina propria invasion was present in 81% of bladder, 60% of ureter, 20% of renal pelvis, and 100% of prostatic urethra cases. Muscularis propria invasion was identified in 19% of bladder, 14% of ureter, and 20% of renal pelvis cases. Urothelial carcinoma invaded periureteric fat in 29% of ureter cases and invaded the renal parenchyma in 60% of renal pelvis cases. Clinical follow-up was available for 77 of 82 (94%) patients with a mean duration of 18 months. Recurrent urothelial carcinoma persisted in 63 of 82 (77%) patients, 16 of 82 (19%) progressed with metastatic disease, and 20 of 77 (26%) patients with bladder involvement died of disease. This study further emphasizes the importance of distinguishing these tumors from benign mimickers of urothelial carcinoma. Recognition of invasive foci is also critical in view of the potentially high frequency of recurrence and the possibility of advanced disease in a subset of these patients.

The Revolution in Medical Education.

Medical education has been gradually evolving for hundreds of years, but educators are now seeking to identify ways to prepare students for the future of health care delivery. Medical education reform today focuses on creating entirely new models and is moving away from the traditional, post-Flexnerian organization of the medical school curriculum. Content is now being integrated thematically and presented along interdisciplinary lines with an interdigitation of basic and clinical sciences across all four years. Current trends indicate education should contain elements that produce a physician who is able to improve the quality of health care by taking a humanistic approach to medicine, thinks critically, and participates effectively in multidisciplinary and team approaches to patient care. Ultimately, medical education innovation should recognize the development of a physician is a lifetime process and will approach the formation of physicians from a new paradigm to better serve the educator and prepare the learner for the medical practice of tomorrow.

Extensive and divergent effects of sleep and wakefulness on brain gene expression.

Sleep is present in all species where it has been studied, but its functions remain unknown. To investigate what benefits sleep may bring at the cellular level, we profiled gene expression in awake and sleeping rats by using high-density microarrays. We find that approximately 10% of the transcripts in the cerebral cortex change their expression between day and night and demonstrate that half of them are modulated by sleep and wakefulness independent of time of day. We also show that molecular correlates of sleep are found in the cerebellum, a structure not known for generating sleep rhythms. Finally, we show that different functional categories of genes are selectively associated with sleep and wakefulness. The approximately 100 known genes whose expression increases during sleep provide molecular support for the proposed involvement of sleep in protein synthesis and neural plasticity and point to a novel role for sleep in membrane trafficking and maintenance.