Faculty Bibliography

PURPOSE: To assess the utility of apparent diffusion coefficient (ADC) values obtained from diffusion-weighted imaging (DWI) in distinguishing high-grade bladder cancer with and without metastatic disease. MATERIALS AND METHODS: Seventeen patients with histologically confirmed high-grade bladder cancer who underwent pelvic magnetic resonance imaging (MRI) at 1.5T including DWI using b-values of 0, 400, and 800 sec/mm(2) were assessed. Histologic findings and follow-up imaging were used to establish the reference standard in terms of metastatic disease. Two radiologists independently recorded ADC of all lesions following a training session, with their results averaged. Mann-Whitney U-test, receiver operating characteristic (ROC) curve analysis and intraclass correlation coefficient (ICC) were used for data analysis. RESULTS: Metastatic disease was characterized as present or absent in eight and nine patients, respectively. ADC was significantly lower among cases with metastatic disease than among cases without metastatic disease, both within the entire cohort (1.07 +/- 0.18 x 10(-3) mm(2) /s vs. 1.45 +/- 0.22 x 10(-3) mm(2) /s; P = 0.002) and within the subset of patients with muscle-invasive tumor (1.06 +/- 0.19 x 10(-3) mm(2) /s vs. 1.45 +/- 0.23 x 10(-3) mm(2) /s; P = 0.017). Area under the ROC curve for identifying metastatic disease using ADC was 0.944, with optimal threshold of 1.21 x 10(-3) mm(2) /s, which was associated with a sensitivity of 87.5%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 90.0%. Interreader agreement for ADC was excellent (ICC = 0.91). CONCLUSION: In this preliminary study, ADC was significantly different between cases of high-grade urothelial carcinoma of the bladder with and without metastatic disease. These results may have value in assessing the metastatic potential of patients with localized high-grade tumors of the bladder. J. Magn. Reson. Imaging 2012;. (c) 2012 Wiley Periodicals, Inc.

Mucinous cystadenocarcinomas of the urachus are rare. Mucinous benign or premalignant tumors are even rarer, yet pose a challenge in diagnosis and management. We report a case of a 66-year-old man with lower abdominal pain who had a large cystic tumor at the dome of the bladder. En-bloc resection of the tumor with partial cystectomy revealed mucinous cystadenocarcinoma in situ. We reviewed the characteristics of all seven previously reported cases. These tumors are pre-malignant and can cause significant morbidity and mortality. They need to be treated similar to conventional mucinous cystadenocarcinoma by wide surgical resection and partial cystectomy.

Over the last two decades, there has been a rising incidence of renal tumors, particularly, small renal masses (<4 cm) resulting in a downward size and stage migration. This has brought about a paradigm shift in the management of newly diagnosed renal masses, such that nephron-sparing surgery, minimally invasive techniques, and active surveillance are frequently considered preferable to the historical gold standard of open radical nephrectomy. Population-based cohort studies indicate, however, that the widespread adoption of these techniques has been relatively slow and incomplete leading to significant disparities in the delivery of care throughout the country. Further investigation is required to determine the barriers to diffusion of new techniques and technology as well as to ensure equal access to quality care in the United States.

Although formation of urothelial carcinoma of the bladder (UCB) requires multiple steps and proceeds along divergent pathways, the underlying genetic and molecular determinants for each step and pathway remain undefined. By developing transgenic mice expressing single or combinatorial genetic alterations in urothelium, we demonstrated here that overcoming oncogene-induced compensatory tumor barriers was critical for urothelial tumor initiation. Constitutively active Ha-ras (Ras*) elicited urothelial hyperplasia that was persistent and did not progress to tumors over a 10 months period. This resistance to tumorigenesis coincided with increased expression of p53 and all pRb family proteins. Expression of a Simian virus 40 T antigen (SV40T), which disables p53 and pRb family proteins, in urothelial cells expressing Ras* triggered early-onset, rapidly-growing and high-grade papillary UCB that strongly resembled the human counterpart (pTaG3). Urothelial cells expressing both Ras* and SV40T had defective G(1)/S checkpoint, elevated Ras-GTPase and hyperactivated AKT-mTOR signaling. Inhibition of the AKT-mTOR pathway with rapamycin significantly reduced the size of high-grade papillary UCB but hyperactivated mitogen-activated protein kinase (MAPK). Inhibition of AKT-mTOR, MAPK and STAT3 altogether resulted in much greater tumor reduction and longer survival than did inhibition of AKT-mTOR pathway alone. Our studies provide the first experimental evidence delineating the combinatorial genetic events required for initiating high-grade papillary UCB, a poorly defined and highly challenging clinical entity. Furthermore, they suggest that targeted therapy using a single agent such as rapamycin may not be highly effective in controlling high-grade UCB and that combination therapy employing inhibitors against multiple targets are more likely to achieve desirable therapeutic outcomes.