Recurrent nephrolithiasis associated with atazanavir use.

A 64-year-old man with HIV on antiretroviral therapy (including atazanavir, a protease inhibitor) presented with left flank pain, nausea and vomiting. A kidney stone was suspected, and a CT scan demonstrated left hydronephrosis but failed to demonstrate nephrolithiasis or extrinsic compression. The patient had a ureteral stent placed which relieved his symptoms. A few months later, he underwent left ureteroscopy and a large ureteral calculus was found. The stone was removed and analysis showed 43% atazanavir and 57% calcium oxalate. Several months later, the patient developed flank pain on the opposite side. A renal ultrasound suggested right-sided nephrolithiasis and he subsequently underwent ureteroscopy with laser lithotripsy of two stones. Stone analysis showed that they were composed of 100% atazanavir. This case highlights the fact that patients treated with protease inhibitors remain at risk for developing nephrolithiasis. Ultrasonography can be a useful diagnostic tool in the setting of these radiolucent calculi.

Effect of statin use on outcomes of non-muscle-invasive bladder cancer.

OBJECTIVES: To assess the impact of statin use on outcomes of patients with non-muscle-invasive bladder cancer (NMIBC). To measure the effect of statin use on the efficacy of intravesical bacillus Calmette-Guérin (BCG) therapy. PATIENTS AND METHODS: A retrospective analysis was performed on 1117 patients treated with transurethral resection of the bladder (TURB) for NMIBC at three institutions between 1996 and 2007. Statin use at the time of diagnosis was recorded for each patient. Univariable Cox regression models addressed the association of statin use with disease recurrence, disease progression, cancer-specific mortality and overall mortality in all patients, patients with primary NMIBC, patients not treated with BCG, and patients treated with BCG. RESULTS: Overall, 341 patients (30.5%) used statins and 776 (69.5%) did not. Within a median (interquartile range) follow-up of 62.7 (25.0-110.7) months, 469 patients (42.0%) experienced disease recurrence, 103 (9.2%) progression, 50 (4.5%) cancer-specific mortality, and 299 (26.8%) any-cause mortality. In univariable Cox regression analyses, statin use was not associated with any of these four endpoints (P > 0.05 for all). In subgroup analyses, statin use was also not associated with prognosis in patients with primary NMIBC or patients not receiving BCG (P > 0.05 for all four endpoints). Statin use was not associated with response to BCG (P > 0.05 for all four endpoints). CONCLUSION: Statin users did not experience different outcomes compared with non-users and statin use did not affect the efficacy of BCG immunotherapy; these data do not support modification or discontinuation of statin therapy for patients with NMIBC.

Clinical nodal staging scores for bladder cancer: a proposal for preoperative risk assessment.

BACKGROUND: Radical cystectomy (RC) with pelvic lymph node dissection (LND) is the standard of care for refractory non-muscle-invasive and muscle-invasive bladder cancer. Although consensus exists on the need for LND, its extent is still debated. OBJECTIVE: To develop a model that allows preoperative determination of the minimum number of lymph nodes (LNs) needed to be removed at RC to ensure true nodal status. DESIGN, SETTING, AND PARTICIPANTS: We analyzed data from 4335 patients treated with RC and pelvic LND without neoadjuvant chemotherapy at 12 academic centers located in the United States, Canada, and Europe. MEASUREMENTS: We estimated the sensitivity of pathologic nodal staging using a beta-binomial model and developed clinical (preoperative) nodal staging scores (cNSS), which represent the probability that a patient has LN metastasis as a function of the number of examined nodes. RESULTS AND LIMITATIONS: The probability of missing a positive LN decreased with an increasing number of nodes examined (52% if 3 nodes were examined, 40% if 5 were examined, and 26% if 10 were examined). A cNSS of 90% was achieved by examining 6 nodes for clinical Ta-Tis tumors, 9 nodes for cT1 tumors, and 25 nodes for cT2 tumors. In contrast, examination of 25 nodes provided only 77% cNSS for cT3-T4 tumors. The study is limited due to its retrospective design, its multicenter nature, and a lack of preoperative staging parameters. CONCLUSIONS: Every patient treated with RC for bladder cancer needs an LND to ensure accurate nodal staging. The minimum number of examined LNs for adequate staging depends preoperatively on the clinical T stage. Predictive tools can give a preoperative estimation of the likelihood of nodal metastasis and thereby allow tailored decision-making regarding the extent of LND at RC.

c-kit and ureteral peristalsis.

PURPOSE: c-kit encodes a tyrosine kinase receptor that is required for the differentiation of a wide variety of cells during embryogenesis, including pacemaker cells of the gut. Functional expression of this tyrosine kinase receptor is required for gut peristalsis and c-kit expression has recently been documented in the adult murine urinary tract. In this study we analyzed the temporal onset of c-kit expression during ureter morphogenesis in vivo and determined if c-kit activity is essential for ureteral peristalsis in vitro. MATERIALS AND METHODS: The kidneys and ureters of gestational days 12.5 to 17.5 WT mice were isolated and frozen sections were prepared for analysis of c-kit, alpha-smooth muscle actin and uroplakin expression by immunocytochemical techniques. In addition, ureters were isolated from gestational day 15.5 mouse urogenital systems and cultured at the air/medium interface on 0.4 um pore polycarbonate membrane filters with Dulbecco's modified Eagle's medium/fetal calf serum in the presence or absence of antibodies that inhibit c-kit function. RESULTS: By gestational day 15.5 c-kit expression could be detected in a subset of renal epithelia and cells of the ureteropelvic adventitia. Prominent staining for c-kit was seen in the muscularis propria of the proximal ureter. In vitro studies demonstrated that isolated embryonic ureters acquire the ability to undergo unidirectional contractions after 3 days of culture, which is coincident with up-regulation of c-kit expression. Furthermore, incubation of isolated ureters with antibodies that neutralize c-kit activity markedly altered ureter morphology and peristalsis. CONCLUSIONS: We identified the initial expression and location of c-kit in the embryonic murine upper urinary tract. c-kit expression is up-regulated in the developing ureter prior to the ability of this tissue to undergo unidirectional contractions and c-kit function is required for the peristalsis in vitro.