Preoperative frailty predicts postoperative complications and mortality in urology patients.

PURPOSE: Our objective was to determine the impact of preoperative frailty, as measured by validated Risk Analysis Index (RAI), on the occurrence of postoperative complications after urologic surgeries in a national database comprised of diverse practice groups and cases. STUDY DESIGN: The National Surgical Quality Improvement Program (NSQIP) database was queried from 2005 to 2011 for a list of abdominal, vaginal, transurethral and scrotal urological surgeries using Current Procedural Terminology codes. The study population was subdivided into two groups based on the nature of procedures performed: complex procedures (inpatient) and simple procedures (outpatient). Risk Analysis Index score was calculated using preoperative NSQIP variables to determine preoperative frailty. Major postoperative morbidities (pulmonary, cardiovascular, renal and infectious), mortality, return to operating room, discharge destination and readmission to the hospital were examined. RESULTS: The study identified 42,715 patients who underwent urological procedures, 25,693 complex and 17,022 simple procedures. Mean RAI score (range) was 7.75 (0-53). The majority of patients scored low on the RAI (90.57 % with RAI < 10). As the RAI score increased, there was a significant increase in postoperative complication and mortality rate (both p < 0.0001). Similarly, the rate of return to operating room and hospital readmission rate increased as RAI increased (both p < 0.0001). Additionally, rate of discharge to home decreased. Interestingly, mortality rate in patients with high RAI did not differ comparing simple to complex procedures (p = 0.90), whereas complications were significantly greater in the complex operation (p = 0.01). CONCLUSIONS: Increase in frailty, as measured by RAI score, is associated with increased postoperative complications and mortality. RAI may allow for rapid identification and counseling of patients who are at high risk of adverse perioperative outcomes.

Human prostatic acid phosphatase: structure, function and regulation.

Human prostatic acid phosphatase (PAcP) is a 100 kDa glycoprotein composed of two subunits. Recent advances demonstrate that cellular PAcP (cPAcP) functions as a protein tyrosine phosphatase by dephosphorylating ErbB-2/Neu/HER-2 at the phosphotyrosine residues in prostate cancer (PCa) cells, which results in reduced tumorigenicity. Further, the interaction of cPAcP and ErbB-2 regulates androgen sensitivity of PCa cells. Knockdown of cPAcP expression allows androgen-sensitive PCa cells to develop the castration-resistant phenotype, where cells proliferate under an androgen-reduced condition. Thus, cPAcP has a significant influence on PCa cell growth. Interestingly, promoter analysis suggests that PAcP expression can be regulated by NF-κB, via a novel binding sequence in an androgen-independent manner. Further understanding of PAcP function and regulation of expression will have a significant impact on understanding PCa progression and therapy.

Novel Imidazopyridine Derivatives Possess Anti-Tumor Effect on Human Castration-Resistant Prostate Cancer Cells.

Prostate cancer (PCa) is the second leading cause of cancer-related death afflicting United States males. Most treatments to-date for metastatic PCa include androgen-deprivation therapy and second-generation anti-androgens such as abiraterone acetate and enzalutamide. However, a majority of patients eventually develop resistance to these therapies and relapse into the lethal, castration-resistant form of PCa to which no adequate treatment option remains. Hence, there is an immediate need to develop effective therapeutic agents toward this patient population. Imidazopyridines have recently been shown to possess Akt kinase inhibitory activity; thus in this study, we investigated the inhibitory effect of novel imidazopyridine derivatives HIMP, M-MeI, OMP, and EtOP on different human castration-resistant PCa cells. Among these compounds, HIMP and M-MeI were found to possess selective dose- and time-dependent growth inhibition: they reduced castration-resistant PCa cell proliferation and spared benign prostate epithelial cells. Using LNCaP C-81 cells as the model system, these compounds also reduced colony formation as well as cell adhesion and migration, and M-MeI was the most potent in all studies. Further investigation revealed that while HIMP primarily inhibits PCa cell growth via suppression of PI3K/Akt signaling pathway, M-MeI can inhibit both PI3K/Akt and androgen receptor pathways and arrest cell growth in the G2 phase. Thus, our results indicate the novel compound M-MeI to be a promising candidate for castration-resistant PCa therapy, and future studies investigating the mechanism of imidazopyridine inhibition may aid to the development of effective anti-PCa agents.

Assessing preoperative frailty utilizing validated geriatric mortality calculators and their association with postoperative hip fracture mortality risk.

INTRODUCTION: End-of-life surgical care is a major concern with a significant number of operations performed within the last year of life; surgery for hip fractures is a prime example. Unfortunately, no simple objective tool exists to assess life expectancy in the postoperative period. The goal of our study was to analyze 2 simple geriatric life expectancy calculators to compare with the current Veterans Affairs Surgical Quality Improvement Program (VASQIP) postoperative 30-day mortality calculator. METHODS: This retrospective study assessed the utility of 3 validated calculators in 47 hip fracture repairs from July 2009 to May 2011. The tools included: 30-day VASQIP mortality calculator, 6-month Minimum Data Set Mortality Risk Index-Revised (MMRI-R), and Four-Year Mortality Index. The VASQIP calculator requires chart review, Current Procedural Terminology (CPT) codes, and laboratory analysis, whereas the mortality risk indices require simple patient questioning if prospective or simple chart review if retrospective. Scoring was performed and mortality risk was compared between survivors and nonsurvivors. RESULTS: A total of 47 hip fractures were repaired during the study period with 37 survivors and 10 nonsurvivors. In all, 7 died within 30 days, 2 died within 6 months, and 1 died greater than 6 months after surgery. The mean age (standard deviation [SD]) of all patients undergoing hip fracture repair was 73.6 (13.3) years. The VASQIP calculator mean (SD) 30-day mortality risk was 10.4% (5.4) for nonsurvivors compared to survivors 4.3% (5.5), P < .003; the MMRI-R mean (SD) mortality risk was 35.8% (15.4) for nonsurvivors compared to survivors 14.7% (9.5), P < .001; the Four-Year Mortality Index mean (SD) mortality risk was 60.9% (16.9) for nonsurvivors compared to survivors 48.9% (24.4), P < .09. CONCLUSION: Overall, the VASQIP 30-day and MMRI-R 6-month mortality calculators showed significant differences in mortality risk between survivors versus nonsurvivors in a population with hip fracture. In contrast, the Four-Year Mortality calculator may not sufficiently discriminate operative risk. The easily obtained MMRI-R has the potential to provide information on short-term postoperative mortality risk.