[Show abstract][Hide abstract] ABSTRACT: High-risk non-muscle invasive bladder cancer (NMIBC) is associated with higher rates of recurrence and progression. Molecular markers within aberrant signaling pathways in cancer need further evaluation of their role as prognostic indicators and potential future targets for prevention of recurrence. Our objective was to investigate the role of the mammalian target of rapamycin (mTOR) signaling pathway on the stage and outcome of patients with high-risk NMIBC. Tissue microarrays were built from archival bladder tumor specimens (n = 142). Various clinicopathologic variables were collected retrospectively from patients treated with transurethral resection. Immunohistochemical staining was performed for phosphatase and tensin homolog, phosphorylated Akt, phosphorylated mTOR, phosphorylated S6 (p-S6), eukaryotic translation initiation factor 4E-binding protein-1, and p27. Multivariate analysis using Cox regression models addressed recurrence-free survival (RFS), progression-free survival, and worsening-free survival. In multivariate analysis, p-S6 was an independent predictor of shorter RFS (hazard ratio, 3.55; 95% CI, 1.31-9.64). Expression of p27 was inversely correlated with RFS (hazard ratio, 0.27; 95% CI, 0.10-0.74). Low levels of phosphatase and tensin homolog expression were associated with worsening-free survival (P < .03). None of the markers showed correlation with progression-free survival. Our results demonstrate that activation of the mTOR pathway, as assessed by p-S6 and expression of p27, might be used to provide prognostic information, particularly as a predictor of recurrence among patients with high-risk NMIBC.
Human pathology 04/2013; 44(9). DOI:10.1016/j.humpath.2012.11.026 · 2.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess outcome in patients with T1 high-grade (T1HG) bladder cancer treated at a single academic institution and to determine the prognostic factors that can help in counselling patients towards early cystectomy.
Records of 2570 patients with bladder cancer treated from 1995 to 2005 were reviewed. Only patients diagnosed with T1HG disease were included in the analysis. Collected variables included various clinicopathological parameters, use of statins, smoking, as well as dates of recurrence, progression, radical cystectomy and death. Recurrence-free survival (RFS) and worsening-free survival (WFS) were analyzed. Multivariate Cox proportional regression analysis was employed to verify the prognostic significance of various variables.
In total, 278 (10.8%) patients were identified as having T1HG disease on transurethral resection. 66% of patients who recurred, and 36.3% developed stage progression after a median (range) follow-up of 3 (0.1-15.4) years. 30% patients who underwent radical cystectomy, and 9% were dead of disease. The 5-year RFS and WFS rates were 26.6% and 49.4%, respectively. On multivariate analysis, only non-trigonal tumour location, restaging transurethral resection, history of previous carcinoma not invading bladder muscle and adjuvant bacille Calmette-Guérin (BCG) therapy were significantly associated with prolonged RFS, whereas papillary tumour architecture, history of previous carcinoma not invading bladder muscle and adjuvant BCG therapy were significantly associated with prolonged WFS.
Patients with T1HG bladder cancer are at a significant risk of progression and death from disease. Primary tumours, sessile architecture and trigonal location are factors associated with a worse outcome and may be used to counsel patients towards early cystectomy.
BJU International 08/2011; 109(7):1026-30. DOI:10.1111/j.1464-410X.2011.10462.x · 3.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although recommended management strategy for nonmuscle-invasive bladder cancer (NMIBC) involves a single postoperative intravesical therapy with mitomycin C (MMC), it is uncommonly used among urologists, in part because of potential increased costs. Our objective was to perform a 5-year cost analysis of this strategy within a single-provider health care environment.
A decision-analytic model was used. Input estimates for 5-year recurrence rates (50%) and MMC efficacy (absolute risk reduction of 17% and 12%) were identified via a systematic literature search and data from 2 meta-analyses. Direct costs included physician fees, MMC drug and preparation costs, transurethral bladder tumor resection (TURBT), and cystoscopy, as well as institutional hospital fees. Indirect societal costs such as work absences and productivity loss were not considered. The model was limited to a 5-year follow-up period with the following assumptions: similar rates of progression, constant recurrence rates, and no cross-over between groups.
Overall 5-year analysis reveals that TURBT plus MMC strategy is not associated with increased costs; it saves the Medicare system $148/patient compared with TURBT alone. Calculated differences took into account avoidance of cystoscopic surveillance, urinary cytology, and reoperative and follow-up costs associated with multiple recurrences. Analysis revealed dominance of MMC usage over TURBT alone as early as 4 years from surgery.
Routine usage of MMC after TURBT is not associated with increased costs to the health care system. In fact, there is a significant cost savings. Nonquantified patient quality of life benefits and secondary societal advantages of gained wages and productivity owing to decreases in recurrence and surgery would further increase the cost savings.
[Show abstract][Hide abstract] ABSTRACT: To examine and compare the left and right spermatic cord arterial and lymphatic anatomy identified at primary and redo microsurgical subinguinal varicocelectomy.
We reviewed the operative reports of 335 consecutive microsurgical varicocelectomies performed by a single surgeon: 325 primary repairs and 10 reoperations. We recorded number of testicular arteries (internal and external spermatic) and lymphatic channels preserved at subinguinal microsurgical varicocelectomy, and evaluated the relationship between the right and left vascular anatomy at bilateral varicocelectomy.
A total of 235 left-sided and 90 bilateral primary repairs were performed. A mean (+/-standard deviation) number of 2.4+/-1.0 arteries and 4.6+/-1.5 lymphatics were identified during the left-sided repairs. For bilateral repairs, there were 2.4+/-0.9 arteries and 4.4+/-1.2 lymphatics on the left and 2.2+/-0.9 arteries and 4.2+/-1.3 lymphatics on the right with a significant correlation between the number of right and left internal spermatic arteries (r=0.42). For the cohort of secondary (redo) varicocelectomies, we identified 2.3+/-0.6 arteries and 4.8+/-1.6 lymphatic channels (not significantly different from the primary varicocelectomy cohorts).
The number of arteries and lymphatics preserved at microsurgical varicocelectomy is highly variable, but there is some similarity in the microanatomy of the right and left spermatic cords at the level of the external inguinal ring. The data also suggest that the number of arteries and lymphatic channels identified at a redo varicocelectomy is comparable to that observed during a primary varicocelectomy.