Purpose: NK cells exhibit cytotoxicity against neuroblastoma. Gene polymorphisms governing NK cell function, therefore, may influence prognosis. Two highly polymorphic genetic loci instrumental in determining NK cell responses encode the NK cell killer immunoglobulin-like receptors (KIR) and their class I human leukocyte antigen (HLA) ligands. We hypothesized that patients with a "missing ligand" KIR-HLA compound genotype may uniquely benefit from autologous hematopoietic stem cell transplantation (HSCT). Experimental Design: One hundred sixty-nine patients treated with autologous HSCT for stage IV neuroblastoma underwent KIR and HLA genotyping. Patients were segregated according to the presence or absence of HLA ligands for autologous inhibitory KIR. Univariate and multivariate analyses were done for overall and progression-free survival. Results: Sixty-four percent of patients lacked one or more HLA ligands for inhibitory KIR. Patients lacking a HLA ligand had a 46% lower risk of death [hazard ratio, 0.54; 95% confidence interval (95% CI), 0.35-0.85; P = 0.007] and a 34% lower risk of progression (hazard ratio, 0.66; 95% CI, 0.44-1.0; P = 0.047) at 3 years compared with patients who possessed all ligands for his/her inhibitory KIR. Among all KIR-HLA combinations, 16 patients lacking the HLA-C1 ligand for KIR2DL2/KIR2DL3 experienced the highest 3-year survival rate of 81% (95% CI, 64-100). Survival was more strongly associated with "missing ligand" than with tumor MYCN gene amplification. Conclusion: KIR-HLA immunogenetics represents a novel prognostic marker for patients undergoing autologous HSCT for high-risk neuroblastoma. (Clin Cancer Res 2009;15(23):7330-4) Neuroblastoma is the most frequently diagnosed cancer in infants and is the most common extracranial solid tumor in childhood (1). Prognosis varies, and risk assessment is based on several clinical and biological features, including age, stage at diagnosis, histopathology, and biomarkers of tumor aggressiveness (MYCN status, histology, and DNA ploidy; refs. 2,3). The risk of tumor progression likely depends not only on tumor biology but also on the host immune response. NK cells are capable of inhibiting colony formation of human neuroblastoma cells (4-7), and infusion of NK cells into nonobese diabetic/severe combined immunodeficient mice bearing human metastatic neuroblastoma leads to a significant improvement in overall survival (4). Based on recent advances linking NK cell function to NK cell genetics (8-11), we hypothesized that variations in genes responsible for regulating NK function may affect clinical outcomes for patients with neuroblastoma.The killer immunoglobulin-like receptor (KIR) gene cluster consists of 15 genes that encode both inhibitory and activating NK cell surface receptors instrumental in governing NK cell function. The similarly polymorphic human leukocyte antigen (HLA) class I gene loci encode three ligand groups for inhibitory KIR: HLA for KIR2DL2/KIR2DL3, HLA for KIR2DL1, and HLA for 12KIR3DL1. Ligation of inhi...

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Stress urinary incontinence (SUI) is a major problem affecting more than 20% of the nation's female population, with increasing prevalence as our population continues to age. Incontinence places a great burden on individuals, and the economic effect is large. Stress urinary incontinence occurs when there is involuntary leakage of urine during coughing, laughing, sneezing, or physical activity. It can be diagnosed during physical examination and by using low-cost office diagnostics. Although nonsurgical treatments provide some benefit, surgical interventions have demonstrated superiority with respect to subjective and objective cure and better long-term improvement. Corrective surgeries for SUI can be grouped into four categories: 1) slings (midurethral slings and slings placed at the ureterovesical junction), 2) retropubic urethropexy, 3) urethral bulking agents, and 4) artificial sphincters. The success and failure of each approach needs to be assessed in the context of individual patients and their circumstances. Slings and retropubic urethropexy are considered first-line surgical options. Since the advent of minimally invasive retropubic midurethral slings such as the tension-free vaginal tape, transobturator tension-free vaginal tape, and single-incision sling, retropubic urethropexy have fallen out of favor. Warnings about mesh use may contribute to a resurgence of retropubic urethropexy procedures such as the Burch procedure. A Burch procedure should still be considered for patients who have an aversion to mesh or if they are undergoing concurrent abdominal approach surgery. Urethral bulking agents are usually reserved for patients with a fixed, nonmobile urethra who cannot tolerate an operative experience or have failed previous antiincontinence procedures. Artificial sphincters should be considered an operation of last resort.

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