Functional p53 mutation as a molecular determinant of paclitaxel and gemcitabine susceptibility in human bladder cancer.

PURPOSE: Paclitaxel and gemcitabine are promising new agents for treatment of human bladder cancer. We determine how the presence or absence of p53 function impacts the cytotoxic effects of these chemotherapeutic agents in human bladder cancer. MATERIALS AND METHODS: The J82 human bladder cancer (TCC) cell line was transfected with a temperature sensitive p53 (tsp53) mutant that functions as mutated p53 at 37C but functions as wild-type (normal) p53 at 32C. Susceptibility of these inducible p53 TCC cells to paclitaxel and gemcitabine induced cytotoxicity was evaluated and kill significance determined between sub-lethal and lethal doses. RESULTS: Significant paclitaxel dose dependent cytotoxicity was observed in J82 TCC cells lacking normal p53 and tsp53 transfected cells at 37C, which was the mutant p53 temperature in transfectants between maximal and minimal kill concentrations for either (p <0.001). Likewise, significant cytotoxicity was observed in parental J82 TCC at 32C (p <0.001), while restoration of p53 function in tsp53 transfected cells on shift to 32C abrogated significant dose dependent cytotoxicity. Gemcitabine caused significant cell death in the cell lines incubated at either temperature and, thus, was equally effective regardless of cellular p53 function (p <0.001, respectively). CONCLUSIONS: Paclitaxel requires functionally mutated p53 to induce cell death in human bladder cells, indicating that it may be more effective against TCC with p53 mutations than against TCC, which lacks p53 abnormalities, while gemcitabine is effective regardless of p53 function. These findings provide a rationale for selecting chemotherapy based on the p53 status of individual bladder cancers.

Evaluation and management of traumatic posterior urethral disruption with flexible cystourethroscopy.

BACKGROUND: We sought to consolidate evaluation and management of traumatic urethral disruption using cystourethroscopic evaluation without retrograde urethrogram or suprapubic cystostomy placement. METHODS: We review our experience with initial flexible cystourethroscopic evaluation of suspected urethral injury from blunt trauma with placement of a Council urethral catheter to provide primary endoscopic realignment of the urethra. RESULTS: Access into the bladder was achieved in 8 of 10 patients. After a mean follow-up of 18 months (range, 9-27 months) in the six living patients, only three have required treatment for urethral stricture--direct vision internal urethrotomy in two, and open perineal urethroplasty in one. Urinary continence has been achieved in five of six patients. CONCLUSION: Primary flexible cystourethroscopy with placement of a urethral catheter streamlines evaluation of traumatic posterior urethral injury. In the presence of partial disruption it provided stricture-free outcomes in three of three surviving patients.

Bladder tumor detection at virtual cystoscopy.

PURPOSE: To investigate the utility of computed tomographic (CT) virtual cystoscopy in the detection of bladder tumors. MATERIALS AND METHODS: Twenty-six patients suspected or known to have bladder neoplasms underwent CT virtual and conventional cystoscopy. The bladder was insufflated with carbon dioxide through a Foley catheter. Helical CT of the bladder was then performed. The data were downloaded to a workstation for interactive intraluminal navigation. Two radiologists blinded to the results of conventional cystoscopy independently reviewed the transverse and virtual images, with consensus readings for cases with discrepant results. RESULTS: Thirty-six (90%) of 40 bladder lesions proved at conventional cystoscopy were detected with a combination of transverse and virtual images. Four (10%) of 40 bladder lesions, all smaller than 5 mm, were undetected. Transverse and virtual images were complementary, since six polypoid lesions smaller than 5 mm depicted on the virtual images were not seen on the transverse images. In contrast, areas of wall thickening were more readily appreciated on transverse images. CT with patients in both supine and prone positions was necessary, since seven (19%) and five (14%) of 36 lesions were seen only on supine and prone images, respectively. CONCLUSION: CT virtual cystoscopy is a promising technique for use in bladder tumor detection of lesions larger than 5 mm. Optimal evaluation requires adequate bladder distention with the patient in both supine and prone positions and interpretation of both transverse and virtual images.